Skip to main content
SpringerLink
Log in

Regulation of Interleukin-10 Expression

  • Chapter
  • First Online:
Regulation of Cytokine Gene Expression in Immunity and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 941))

Abstract

Interleukin (IL)-10 is an essential anti-inflammatory cytokine that plays important roles as a negative regulator of immune responses to microbial antigens. Loss of IL-10 results in the spontaneous development of inflammatory bowel disease as a consequence of an excessive immune response to the gut microbiota. IL-10 also functions to prevent excessive inflammation during the course of infection. IL-10 can be produced in response to pro-inflammatory signals by virtually all immune cells, including T cells, B cells, macrophages, and dendritic cells. Given its function in maintaining the delicate balance between effective immunity and tissue protection, it is evident that IL-10 expression is highly dynamic and needs to be tightly regulated. The transcriptional regulation of IL-10 production in myeloid cells and T cells is the topic of this review. Drivers of IL-10 expression as well as their downstream signaling pathways and transcription factors will be discussed. We will examine in more detail how various signals in CD4+ T cells converge on common transcriptional circuits, which fine-tune IL-10 expression in a context-dependent manner.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Agrawal S, Gupta S. TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors. J Clin Immunol. 2011;31(1):89–98.

    Article  CAS  PubMed  Google Scholar 

  2. Agrawal S, et al. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol. 2003;171(10):4984–9.

    Article  CAS  PubMed  Google Scholar 

  3. Ahyi A-NN, et al. IFN regulatory factor 4 regulates the expression of a subset of Th2 cytokines. J Immunol. 2009;183(3):1598–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499–511.

    Article  CAS  PubMed  Google Scholar 

  5. Aman MJ, et al. Interferon-alpha stimulates production of interleukin-10 in activated CD4+ T cells and monocytes. Blood. 1996;87(11):4731–6.

    CAS  PubMed  Google Scholar 

  6. Amsen D, Antov A, Flavell RA. The different faces of Notch in T-helper-cell differentiation. Nat Rev Immunol. 2009;9(2):116–24.

    Article  CAS  PubMed  Google Scholar 

  7. Ananieva O, et al. The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling. Nat Immunol. 2008;9(9):1028–36.

    Article  CAS  PubMed  Google Scholar 

  8. Anderson CF, et al. CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med. 2007;204(2):285–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Anderson CF, et al. IL-27 regulates IL-10 and IL-17 from CD4+ cells in nonhealing Leishmania major infection. J Immunol. 2009;183(7):4619–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Apetoh L, et al. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol. 2010;11(9):854–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Awasthi A, et al. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007;8(12):1380–9.

    Article  CAS  PubMed  Google Scholar 

  12. Banerjee A, et al. Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells. Proc Natl Acad Sci U S A. 2006;103(9):3274–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Barthlott T, et al. CD25+ CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production. Int Immunol. 2005;17(3):279–88.

    Article  CAS  PubMed  Google Scholar 

  14. Batten M, et al. Cutting edge: IL-27 is a potent inducer of IL-10 but not FoxP3 in murine T cells. J Immunol. 2008;180(5):2752–6.

    Article  CAS  PubMed  Google Scholar 

  15. Bauquet AT, et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol. 2009;10(2):167–75.

    Article  CAS  PubMed  Google Scholar 

  16. Berg DJ, et al. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J Clin Invest. 1995;96(5):2339–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Blokzijl A, Dijke Ten P, Ibáñez CF. Physical and functional interaction between GATA-3 and Smad3 allows TGF-beta regulation of GATA target genes. Curr Biol. 2002;12(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  18. Boonstra A, et al. Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals. J Immunol. 2006;177(11):7551–8.

    Article  CAS  PubMed  Google Scholar 

  19. Brewer G, et al. Increased interleukin-10 mRNA stability in melanoma cells is associated with decreased levels of A + U-rich element binding factor AUF1. J Interf Cytokine Res. 2003;23(10):553–64.

    Article  CAS  Google Scholar 

  20. Brightbill HD, et al. A prominent role for Sp1 during lipopolysaccharide-mediated induction of the IL-10 promoter in macrophages. J Immunol. 2000;164(4):1940–51.

    Article  CAS  PubMed  Google Scholar 

  21. Brown CY, et al. Differential regulation of the stability of cytokine mRNAs in lipopolysaccharide-activated blood monocytes in response to interleukin-10. J Biol Chem. 1996;271(33):20108–12.

    Article  CAS  PubMed  Google Scholar 

  22. Cao S, et al. NF-kappaB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. J Biol Chem. 2006;281(36):26041–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cao S, et al. The protooncogene c-Maf is an essential transcription factor for IL-10 gene expression in macrophages. J Immunol. 2005;174(6):3484–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Carballo E, Lai WS, Blackshear PJ. Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. Blood. 2000;95(6):1891–9.

    CAS  PubMed  Google Scholar 

  25. Carballo E, Lai WS, Blackshear PJ. Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science. 1998;281(5379):1001–5.

    Article  CAS  PubMed  Google Scholar 

  26. Chakrabarti A, et al. Protein kinase R-dependent regulation of interleukin-10 in response to double-stranded RNA. J Biol Chem. 2008;283(37):25132–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chang EY, et al. Cutting edge: involvement of the type I IFN production and signaling pathway in lipopolysaccharide-induced IL-10 production. J Immunol. 2007;178(11):6705–9.

    Article  CAS  PubMed  Google Scholar 

  28. Chang H-D, et al. Expression of IL-10 in Th memory lymphocytes is conditional on IL-12 or IL-4, unless the IL-10 gene is imprinted by GATA-3. Eur J Immunol. 2007;37(3):807–17.

    Article  CAS  PubMed  Google Scholar 

  29. Chaudhry A, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34(4):566–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chi H, et al. Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc Natl Acad Sci U S A. 2006;103(7):2274–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ciofani M, et al. A validated regulatory network for Th17 cell specification. Cell. 2012;151(2):289–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Corre B, et al. Type I interferon potentiates T-cell receptor mediated induction of IL-10-producing CD4+ T cells. Eur J Immunol. 2013;43(10):2730–40.

    Article  CAS  PubMed  Google Scholar 

  33. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180(9):5771–7.

    Article  CAS  PubMed  Google Scholar 

  34. Creery WD, et al. Differential modulation of B7-1 and B7-2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype. Eur J Immunol. 1996;26(6):1273–7.

    Article  CAS  PubMed  Google Scholar 

  35. Cretney, E. et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells. Nat Immunol. 2011;12(4):304–11.

    Google Scholar 

  36. Cretney E, Kallies A, Nutt SL. Differentiation and function of Foxp3(+) effector regulatory T cells. Trends Immunol. 2012;34(2):74–80.

    Article  PubMed  CAS  Google Scholar 

  37. D’Addario M, Arora PD, McCulloch CA. Role of p38 in stress activation of Sp1. Gene. 2006;379:51–61.

    Article  PubMed  CAS  Google Scholar 

  38. D’Andrea A, et al. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med. 1993;178(3):1041–8.

    Article  PubMed  Google Scholar 

  39. Dardalhon V, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells, and together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol. 2008;9(12):1347–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. de Waal-Malefyt R, Abrams J, et al. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991;174(5):1209–20.

    Article  PubMed  Google Scholar 

  41. de Waal-Malefyt R, Haanen J, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991;174(4):915–24.

    Article  PubMed  Google Scholar 

  42. Dennehy KM, et al. Reciprocal regulation of IL-23 and IL-12 following co-activation of Dectin-1 and TLR signaling pathways. Eur J Immunol. 2009;39(5):1379–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Denning TL, et al. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol. 2007;8(10):1086–94.

    Article  CAS  PubMed  Google Scholar 

  44. Dillon S, et al. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol. 2004;172(8):4733–43.

    Article  CAS  PubMed  Google Scholar 

  45. Dillon S, et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest. 2006;116(4):916–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dong C, Davis R, Flavell R. Map kinases in the immune response. Annu Rev Immunol. 2002;20:55–72.

    Article  CAS  PubMed  Google Scholar 

  47. Edwards AD, et al. Microbial recognition via Toll-like receptor-dependent and -independent pathways determines the cytokine response of murine dendritic cell subsets to CD40 triggering. J Immunol. 2002;169(7):3652–60.

    Article  CAS  PubMed  Google Scholar 

  48. Eidenschenk C, et al. Role of IL-22 in microbial host defense. Curr Top Microbiol Immunol. 2014;380(Chapter 10):213–36.

    CAS  PubMed  Google Scholar 

  49. Elcombe SE, et al. Dectin-1 regulates IL-10 production via a MSK1/2 and CREB dependent pathway and promotes the induction of regulatory macrophage markers. R. Lang, ed. PLoS One. 2013;8(3):e60086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Finbloom DS, Winestock KD. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995;155(3):1079–90.

    CAS  PubMed  Google Scholar 

  51. Fiorentino DF, et al. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991;147(11):3815–22.

    CAS  PubMed  Google Scholar 

  52. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170(6):2081–95.

    Article  CAS  PubMed  Google Scholar 

  53. Fitzgerald DC, et al. Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol. 2007;8(12):1372–9.

    Article  CAS  PubMed  Google Scholar 

  54. Foey AD, et al. Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of the p38 and p42/44 mitogen-activated protein kinases. J Immunol. 1998;160(2):920–8.

    CAS  PubMed  Google Scholar 

  55. Freitas do Rosário AP, et al. IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. J Immunol. 2012;188(3):1178–90.

    Article  PubMed  CAS  Google Scholar 

  56. Fujita S, et al. Regulatory dendritic cells act as regulators of acute lethal systemic inflammatory response. Blood. 2006;107(9):3656–64.

    Article  CAS  PubMed  Google Scholar 

  57. Gaba A, et al. Cutting edge: IL-10-mediated tristetraprolin induction is part of a feedback loop that controls macrophage STAT3 activation and cytokine production. J Immunol. 2012;189(5):2089–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gandhi R, et al. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol. 2010;11(9):846–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Geijtenbeek TBH, et al. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med. 2003;197(1):7–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gerosa F, et al. Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10. J Exp Med. 1996;183(6):2559–69.

    Article  CAS  PubMed  Google Scholar 

  61. Ghoreschi K, et al. Generation of pathogenic T(H) 17 cells in the absence of TGF-β signalling. Nature. 2010;467(7318):967–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Giordani L, et al. IFN-alpha amplifies human naive B cell TLR-9-mediated activation and Ig production. J Leukoc Biol. 2009;86(2):261–71.

    Article  CAS  PubMed  Google Scholar 

  63. Glasmacher E, et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012;338(6109):975–80.

    Article  CAS  PubMed  Google Scholar 

  64. Glocker E-O, et al. IL-10 and IL-10 receptor defects in humans. Ann N Y Acad Sci. 2011;1246:102–7.

    Article  CAS  PubMed  Google Scholar 

  65. Groux H, et al. Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med. 1996;184(1):19–29.

    Article  CAS  PubMed  Google Scholar 

  66. Guarda G, et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity. 2011;34(2):213–23.

    Article  CAS  PubMed  Google Scholar 

  67. Hadis U, et al. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity. 2011;34(2):237–46.

    Article  CAS  PubMed  Google Scholar 

  68. Häcker H, et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature. 2006;439(7073):204–7.

    Article  PubMed  CAS  Google Scholar 

  69. Higgins SC, et al. Toll-like receptor 4-mediated innate IL-10 activates antigen-specific regulatory T cells and confers resistance to Bordetella pertussis by inhibiting inflammatory pathology. J Immunol. 2003;171(6):3119–27.

    Article  CAS  PubMed  Google Scholar 

  70. Ho AS, et al. Functional regions of the mouse interleukin-10 receptor cytoplasmic domain. Mol Cell Biol. 1995;15(9):5043–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hoshi N, et al. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nat Commun. 2012;3:1120.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Hu X, et al. IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins. Immunity. 2006;24(5):563–74.

    Article  CAS  PubMed  Google Scholar 

  73. Hunter CA, Kastelein R. Interleukin-27: balancing protective and pathological immunity. Immunity. 2012;37(6):960–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Im S-H, et al. Chromatin-level regulation of the IL10 gene in T cells. J Biol Chem. 2004;279(45):46818–25.

    Article  CAS  PubMed  Google Scholar 

  75. Ivanov P, Anderson P. Post-transcriptional regulatory networks in immunity. Immunol Rev. 2013;253(1):253–72.

    Article  PubMed  CAS  Google Scholar 

  76. Iwasaki Y, et al. Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells. Eur J Immunol. 2013;43(4):1063–73.

    Article  CAS  PubMed  Google Scholar 

  77. Jankovic D, et al. Conventional T-bet(+)Foxp3(−) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med. 2007;204(2):273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jarnicki AG, et al. Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics. J Immunol. 2008;180(6):3797–806.

    Article  CAS  PubMed  Google Scholar 

  79. Jones EA, Flavell RA. Distal enhancer elements transcribe intergenic RNA in the IL-10 family gene cluster. J Immunol. 2005;175(11):7437–46.

    Article  CAS  PubMed  Google Scholar 

  80. Kaiser F, et al. TPL-2 negatively regulates interferon-beta production in macrophages and myeloid dendritic cells. J Exp Med. 2009;206(9):1863–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kallies A, Hawkins E, Belz G, Metcalf D, Hommel M, Corcoran L, Hodgkin P, Nutt S. Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance. Nat Immunol. 2006;7(5):466–74.

    Article  CAS  PubMed  Google Scholar 

  82. Kanters E, et al. Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003;112(8):1176–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kassner N, et al. Cutting edge: plasmacytoid dendritic cells induce IL-10 production in T cells via the delta-like-4/Notch axis. J Immunol. 2010;184(2):550–4.

    Article  CAS  PubMed  Google Scholar 

  84. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol. 2007;25:221–42.

    Article  CAS  PubMed  Google Scholar 

  85. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84.

    Article  CAS  PubMed  Google Scholar 

  86. Kim C, et al. The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression. Nat Immunol. 2008;9(9):1019–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kim JI, et al. The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity. 1999;10(6):745–51.

    Article  CAS  PubMed  Google Scholar 

  88. Kim JM, et al. Structure of the mouse IL-10 gene and chromosomal localization of the mouse and human genes. J Immunol. 1992;148(11):3618–23.

    CAS  PubMed  Google Scholar 

  89. Kim L, et al. p38 MAPK autophosphorylation drives macrophage IL-12 production during intracellular infection. J Immunol. 2005;174(7):4178–84.

    Article  CAS  PubMed  Google Scholar 

  90. Kimura A, et al. Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses. J Exp Med. 2009;206(9):2027–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kitani A, et al. Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med. 2003;198(8):1179–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kotenko SV, et al. Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J. 1997;16(19):5894–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kratochvill F, et al. Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation. Mol Syst Biol. 2011;7(1):560.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Krausgruber T, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011;12(3):231–8.

    Article  CAS  PubMed  Google Scholar 

  95. Kühn R, et al. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75(2):263–74.

    Article  PubMed  Google Scholar 

  96. de La Rosa M, et al. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. European J Immunol. 2004;34(9):2480–8.

    Article  CAS  Google Scholar 

  97. Lampropoulou V, et al. TLR-activated B cells suppress T cell-mediated autoimmunity. J Immunol. 2008;180(7):4763–73.

    Article  CAS  PubMed  Google Scholar 

  98. Lee C-G, et al. A distal cis-regulatory element, CNS-9, controls NFAT1 and IRF4-mediated IL-10 gene activation in T helper cells. Mol Immunol. 2009;46(4):613–21.

    Article  CAS  PubMed  Google Scholar 

  99. Lee C-G, et al. Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells. J Immunol. 2012;188(5):2244–53.

    Article  CAS  PubMed  Google Scholar 

  100. Levings MK, et al. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol. 2001;166(9):5530–9.

    Article  CAS  PubMed  Google Scholar 

  101. Li MO, Flavell RA. Contextual regulation of inflammation: a duet by transforming growth factor-beta and interleukin-10. Immunity. 2008;28(4):468–76.

    Article  PubMed  CAS  Google Scholar 

  102. Li P, et al. BATF-JUN is critical for IRF4-mediated transcription in T cells. Nature. 2012;490(7421):543–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Liu Y-W, et al. Lipopolysaccharide-induced transcriptional activation of interleukin-10 is mediated by MAPK- and NF-kappaB-induced CCAAT/enhancer-binding protein delta in mouse macrophages. Cell Signal. 2006;18(9):1492–500.

    Article  CAS  PubMed  Google Scholar 

  104. Lucas M, et al. ERK activation following macrophage FcgammaR ligation leads to chromatin modifications at the IL-10 locus. J Immunol. 2005;175(1):469–77.

    Article  CAS  PubMed  Google Scholar 

  105. Ma F, et al. MicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. J Immunol. 2010;184(11):6053–9.

    Article  CAS  PubMed  Google Scholar 

  106. Ma W, et al. The p38 mitogen-activated kinase pathway regulates the human interleukin-10 promoter via the activation of Sp1 transcription factor in lipopolysaccharide-stimulated human macrophages. J Biol Chem. 2001;276(17):13664–74.

    CAS  PubMed  Google Scholar 

  107. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5(6):472–84.

    Article  CAS  PubMed  Google Scholar 

  108. Madan R, et al. Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. J Immunol. 2009;183(4):2312–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Martin M, et al. Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J Immunol. 2003;171(2):717–25.

    Article  CAS  PubMed  Google Scholar 

  110. Martins G, Calame K. Regulation and functions of Blimp-1 in T and B lymphocytes. How TCRS bind MHCS, peptides, and coreceptors. Annu Rev Immunol. 2008;26:133–169.

    Google Scholar 

  111. Martins GA, et al. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat Immunol. 2006;7(5):457–65.

    Article  CAS  PubMed  Google Scholar 

  112. Mayer-Barber KD, et al. Innate and adaptive interferons suppress IL-1α and IL-1β production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection. Immunity. 2011;35(6):1023–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Maynard C, Weaver C. Diversity in the contribution of interleukin-10 to T-cell-mediated immune regulation. Immunol Rev. 2008;226:219–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Maynard CL, et al. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10. Nat Immunol. 2007;8(9):931–41.

    Article  CAS  PubMed  Google Scholar 

  115. McGeachy MJ, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007;8(12):1390–7.

    Article  CAS  PubMed  Google Scholar 

  116. McNab FW, et al. TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production. J Immunol. 2013;191(4):1732–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Meraz MA, et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell. 1996;84(3):431–42.

    Article  CAS  PubMed  Google Scholar 

  118. Meyaard L, et al. IL-12-induced IL-10 production by human T cells as a negative feedback for IL-12-induced immune responses. J Immunol. 1996;156(8):2776–82.

    CAS  PubMed  Google Scholar 

  119. Moore K et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683–765.

    Google Scholar 

  120. Moore KW, et al. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990;248(4960):1230–4.

    Article  CAS  PubMed  Google Scholar 

  121. Motomura Y, et al. The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Nat Immunol. 2011;12(5):450–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Murai M, et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10(11):1178–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Murphy TL, Tussiwand R, Murphy KM. Specificity through cooperation: BATF-IRF interactions control immune-regulatory networks. Nat Rev Immunol. 2013;13(7):499–509.

    Article  CAS  PubMed  Google Scholar 

  124. Murugaiyan G, et al. IL-27 is a key regulator of IL-10 and IL-17 production by human CD4+ T cells. J Immunol. 2009;183(4):2435–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Nandan D, et al. Myeloid cell IL-10 production in response to leishmania involves inactivation of glycogen synthase kinase-3β downstream of phosphatidylinositol-3 kinase. J Immunol. 2012;188(1):367–78.

    Article  CAS  PubMed  Google Scholar 

  126. Neininger A, et al. MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels. J Biol Chem. 2002;277(5):3065–8.

    Article  CAS  PubMed  Google Scholar 

  127. Netea MG, et al. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol. 2004;172(6):3712–8.

    Article  CAS  PubMed  Google Scholar 

  128. Neumann C, et al. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J Exp Med. 2014;204(2):285.

    Google Scholar 

  129. O’Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol. 2007;7(6):425–8.

    Article  PubMed  CAS  Google Scholar 

  130. Ohtani M, et al. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood. 2008;112(3):635–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Ouyang W, et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol. 2011;29(1):71–109.

    Article  CAS  PubMed  Google Scholar 

  132. Pattison MJ, MacKenzie KF, Arthur JSC. Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback. J Immunol. 2012;189(6):2784–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Platzer C, et al. Cyclic adenosine monophosphate-responsive elements are involved in the transcriptional activation of the human IL-10 gene in monocytic cells. Eur J Immunol. 1999;29(10):3098–104.

    Article  CAS  PubMed  Google Scholar 

  134. Pot C, et al. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol. 2009;183(2):797–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Pot C, et al. Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27. Semin Immunol. 2011;23(6):438–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Powell MJ, et al. Posttranscriptional regulation of IL-10 gene expression through sequences in the 3′-untranslated region. J Immunol. 2000;165(1):292–6.

    Article  CAS  PubMed  Google Scholar 

  137. Qin Z, et al. Pivotal advance: Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded microRNA specifically induce IL-6 and IL-10 secretion by macrophages and monocytes. J Leukoc Biol. 2010;87(1):25–34.

    Article  CAS  PubMed  Google Scholar 

  138. Quinn SR, O’Neill LA. The role of microRNAs in the control and mechanism of action of IL-10. Curr Top Microbiol Immunol. 2014;380(Chapter 7):145–55.

    CAS  PubMed  Google Scholar 

  139. Radtke F, Macdonald HR, Tacchini-Cottier F. Regulation of innate and adaptive immunity by Notch. Nat Rev Immunol. 2013;13(6):427–37.

    Article  CAS  PubMed  Google Scholar 

  140. Rakoff-Nahoum S, Hao L, Medzhitov R. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006;25(2):319–29.

    Article  CAS  PubMed  Google Scholar 

  141. Risco A, et al. p38γ and p38δ kinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation. Proc Natl Acad Sci U S A. 2012;109(28):11200–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Roers A, et al. T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J Exp Med. 2004;200(10):1289–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Rogers NC, et al. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 2005;22(4):507–17.

    Article  CAS  PubMed  Google Scholar 

  144. Roncarolo MG, et al. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev. 2006;212:28–50.

    Article  CAS  PubMed  Google Scholar 

  145. Rubtsov YP, et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008;28(4):546–58.

    Article  CAS  PubMed  Google Scholar 

  146. Rutz S, Ouyang W. Regulation of interleukin-10 and interleukin-22 expression in T helper cells. Curr Opin Immunol. 2011;23(5):605–12.

    Article  CAS  PubMed  Google Scholar 

  147. Rutz S, et al. Notch regulates IL-10 production by T helper 1 cells. Proc Natl Acad Sci U S A. 2008;105(9):3497–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Rutz S, et al. Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in T(H)17 cells. Nat Immunol. 2011;12(12):1238–45.

    Article  CAS  PubMed  Google Scholar 

  149. Rutz S, Wang X, Ouyang W. The IL-20 subfamily of cytokines – from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14(12):783–95.

    Article  CAS  PubMed  Google Scholar 

  150. Salehi S, et al. B lymphocyte-induced maturation protein-1 contributes to intestinal mucosa homeostasis by limiting the number of IL-17-producing CD4+ T cells. J Immunol. 2012;189(12):5682–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Salojin KV, et al. Essential role of MAPK phosphatase-1 in the negative control of innate immune responses. J Immunol. 2006;176(3):1899–907.

    Article  CAS  PubMed  Google Scholar 

  152. Sandler H, Stoecklin G. Control of mRNA decay by phosphorylation of tristetraprolin. Biochem Soc Trans. 2008;36(Pt 3):491–6.

    Article  CAS  PubMed  Google Scholar 

  153. Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170–81.

    Article  CAS  PubMed  Google Scholar 

  154. Saraiva M, et al. Identification of a macrophage-specific chromatin signature in the IL-10 locus. J Immunol. 2005;175(2):1041–6.

    Article  CAS  PubMed  Google Scholar 

  155. Saraiva M, et al. Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity. 2009;31(2):209–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Sayi A, et al. TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells. J Immunol. 2011;186(2):878–90.

    Article  CAS  PubMed  Google Scholar 

  157. Schaljo B, et al. Tristetraprolin is required for full anti-inflammatory response of murine macrophages to IL-10. J Immunol. 2009;183(2):1197–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Schuetze N, et al. IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages. Int Immunol. 2005;17(5):649–59.

    Article  CAS  PubMed  Google Scholar 

  159. Schulz EG, et al. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity. 2009;30(5):673–83.

    Article  CAS  PubMed  Google Scholar 

  160. Sellon RK, et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998;66(11):5224–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Sharma A, et al. Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009;106(14):5761–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Shaw MH, et al. Tyk2 negatively regulates adaptive Th1 immunity by mediating IL-10 signaling and promoting IFN-gamma-dependent IL-10 reactivation. J Immunol. 2006;176(12):7263–71.

    Article  CAS  PubMed  Google Scholar 

  163. Sheedy FJ, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 2010;11(2):141–7.

    Article  CAS  PubMed  Google Scholar 

  164. Shoemaker J, Saraiva M, O’Garra A. GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+ T cells. J Immunol. 2006;176(6):3470–9.

    Article  CAS  PubMed  Google Scholar 

  165. Shouval DS, et al. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity. 2014;40(5):706–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Siewe L, et al. Interleukin-10 derived from macrophages and/or neutrophils regulates the inflammatory response to LPS but not the response to CpG DNA. Eur J Immunol. 2006;36(12):3248–55.

    Article  CAS  PubMed  Google Scholar 

  167. Skok J, Poudrier J, Gray D. Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development. J Immunol. 1999;163(8):4284–91.

    CAS  PubMed  Google Scholar 

  168. Slack EC, et al. Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan. Eur J Immunol. 2007;37(6):1600–12.

    Article  CAS  PubMed  Google Scholar 

  169. Spolski R, et al. IL-21 mediates suppressive effects via its induction of IL-10. J Immunol. 2009;182(5):2859–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Staples KJ, et al. IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3. J Immunol. 2007;178(8):4779–85.

    Article  CAS  PubMed  Google Scholar 

  171. Stoecklin G, et al. Genome-wide analysis identifies interleukin-10 mRNA as target of tristetraprolin. J Biol Chem. 2008;283(17):11689–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Stumhofer JS, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol. 2006;7(9):937–45.

    Article  CAS  PubMed  Google Scholar 

  173. Stumhofer JS, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol. 2007;8(12):1363–71.

    Article  CAS  PubMed  Google Scholar 

  174. Sun J, et al. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol. 2011;12(4):327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Takeda K, et al. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity. 1999;10(1):39–49.

    Article  CAS  PubMed  Google Scholar 

  176. Tan JC, et al. Characterization of interleukin-10 receptors on human and mouse cells. J Biol Chem. 1993;268(28):21053–9.

    CAS  PubMed  Google Scholar 

  177. Tan NY, Khachigian LM. Sp1 phosphorylation and its regulation of gene transcription. Mol Cell Biol. 2009;29(10):2483–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Tone M, et al. IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3. J Immunol. 2000;165(1):286–91.

    Article  CAS  PubMed  Google Scholar 

  179. Trandem K, et al. Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis. J Immunol. 2011;186(6):3642–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Trinchieri G. Interleukin-10 production by effector T cells: Th1 cells show self control. J Exp Med. 2007;204(2):239–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Tudor C, et al. The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages. FEBS Lett. 2009;583(12):1933–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Tussiwand R, et al. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature. 2012;490(7421):502–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Uhlig HH, et al. Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. J Immunol. 2006;177(9):5852–60.

    Article  CAS  PubMed  Google Scholar 

  184. Unterberger C, et al. Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene. Mol Immunol. 2008;45(11):3230–7.

    Article  CAS  PubMed  Google Scholar 

  185. Vahedi G, et al. STATs shape the active enhancer landscape of T cell populations. Cell. 2012;151(5):981–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Vasanthakumar A, Kallies A. IL-27 paves different roads to Tr1. Eur J Immunol. 2013;43(4):882–5.

    Article  CAS  PubMed  Google Scholar 

  187. Veldhoen M, et al. Transforming growth factor-beta “reprograms” the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol. 2008;9(12):1341–6.

    Article  CAS  PubMed  Google Scholar 

  188. Villagra A, et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol. 2009;10(1):92–100.

    Article  CAS  PubMed  Google Scholar 

  189. Villarino A, et al. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity. 2003;19(5):645–55.

    Article  CAS  PubMed  Google Scholar 

  190. Voll RE, et al. Immunosuppressive effects of apoptotic cells. Nature. 1997;390(6658):350–1.

    Article  CAS  PubMed  Google Scholar 

  191. Wang Z-Y, et al. Regulation of IL-10 gene expression in Th2 cells by Jun proteins. J Immunol. 2005;174(4):2098–105.

    Article  CAS  PubMed  Google Scholar 

  192. Wei L, et al. Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity. 2010;32(6):840–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Weichhart T, et al. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity. 2008;29(4):565–77.

    Article  CAS  PubMed  Google Scholar 

  194. Willems F, et al. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol. 1994;24(4):1007–9.

    Article  CAS  PubMed  Google Scholar 

  195. Xu J, et al. c-Maf regulates IL-10 expression during Th17 polarization. J Immunol. 2009;182(10):6226–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Yi A-K, et al. Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response. J Immunol. 2002;168(9):4711–20.

    Article  CAS  PubMed  Google Scholar 

  197. Yu H, et al. MKP-1 regulates cytokine mRNA stability through selectively modulation subcellular translocation of AUF1. Cytokine. 2011;56(2):245–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Zhang X, et al. Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells. J Exp Med. 2007;204(5):1107–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Zhang X, Edwards J, Mosser D. Dynamic and transient remodeling of the macrophage IL-10 promoter during transcription. J Immunol. 2006;177(2):1282–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Zhu J et al. Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol. 2004;5(11):1157–65.

    Google Scholar 

  201. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol. 2010;28:445–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Ziegler-Heitbrock L, et al. IFN-alpha induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3. J Immunol. 2003;171(1):285–90.

    Article  CAS  PubMed  Google Scholar 

  203. Zigmond E, et al. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity. 2014;40(5):720–33.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Wenjun Ouyang

    Present address: Present Affiliation: Department of Inflammation and Oncology, Amgen, 1120 Veterans Blvd, South San Francisco, CA, 94080, USA

Authors and Affiliations

  1. Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA

    Sascha Rutz

  2. Department of Immunology, Genentech, South San Francisco, CA, USA

    Wenjun Ouyang

Authors
  1. Sascha Rutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenjun Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sascha Rutz .

Editor information

Editors and Affiliations

  1. State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China

    Xiaojing Ma

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Rutz, S., Ouyang, W. (2016). Regulation of Interleukin-10 Expression. In: Ma, X. (eds) Regulation of Cytokine Gene Expression in Immunity and Diseases. Advances in Experimental Medicine and Biology, vol 941. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0921-5_5

Download citation

Publish with us

Policies and ethics

Search

Navigation