Skip to main content
SpringerLink
Log in

Tuning of inflammatory cytokines and toll-like receptors by TIR8/SIGIRR, a member of the IL-1 receptor family with unique structure and regulation

  • Chapter
Toll-like Receptors in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

  • 654 Accesses

Concluding remarks

Thus, TIR8 represents a negative pathway of regulation of the IL-1R/TLR system, with a unique pattern of expression in epithelial cells and DC, crucial for tuning inflammation at mucosal surfaces, in particular in the gastrointestinal tract. Further research is needed to explore the role of TIR8 in controlling inflammation at other mucosal tissues and to investigate its expression and involvement in the pathogenesis of human diseases, in particular in inflammatory bowel disease.

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 PDF
  • Read on any device
  • Instant download
  • Own it forever
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dinarello CA (1996) Biological basis for IL-1 in disease. Blood 87: 2095–2147

    CAS  PubMed  Google Scholar 

  2. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1: 135–145

    Article  CAS  PubMed  Google Scholar 

  3. O’Neill LA (2002) Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal? Trends Immunol 23: 296–300

    CAS  PubMed  Google Scholar 

  4. Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21: 335–376

    Article  CAS  PubMed  Google Scholar 

  5. Barton GM, Medzhitov R (2003) Toll-like receptor signaling pathways. Science 300: 1524–1525

    Article  CAS  PubMed  Google Scholar 

  6. O’Neill LA, Dinarello CA (2000) The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol Today 21: 206–209

    CAS  PubMed  Google Scholar 

  7. Sweet MJ, Leung BP, Kang D, Sogaard M, Schulz K, Trajkovic V, Campbell CC, Xu D, Liew FY (2001) A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression. J Immunol 166: 6633–6639

    CAS  PubMed  Google Scholar 

  8. Brint EK, Fitzgerald KA, Smith P, Coyle AJ, Gutierrez-Ramos JC, Fallon PG, O’Neill LA (2002) Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction. J Biol Chem 277: 49205–49211

    Article  CAS  PubMed  Google Scholar 

  9. Brint EK, Xu D, Liu H, Dunne A, McKenzie AN, O’Neill LA, Liew FY (2004) ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat Immunol 5: 373–379

    Article  CAS  PubMed  Google Scholar 

  10. Mantovani A, Locati M, Polentarutti N, Vecchi A, Garlanda C (2004) Extracellular and intracellular decoys in the tuning of inflammatory cytokines and Toll-like receptors: the new entry TIR8/SIGIRR. J Leukoc Biol 75: 738–742

    CAS  PubMed  Google Scholar 

  11. Arend WP (1993) Interleukin-1 receptor antagonist. Adv Immunol 54: 167–227

    CAS  PubMed  Google Scholar 

  12. Muzio M, Polentarutti N, Sironi M, Poli G, De Gioia L, Introna M, Mantovani A, Colotta F (1995) Cloning and characterization of a new isoform of the interleukin-1 receptor antagonist. J Exp Med 182: 623–628

    Article  CAS  PubMed  Google Scholar 

  13. Colotta F, Re F, Muzio M, Bertini R, Polentarutti N, Sironi M, Giri JG, Dower SK, Sims JE, Mantovani A (1993) Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science 261: 472–475

    CAS  PubMed  Google Scholar 

  14. Colotta F, Dower SK, Sims JE, Mantovani A (1994) The type II ‘decoy’ receptor: novel regulatory pathway for interleukin-1. Immunol Today 15: 562–566

    Article  CAS  PubMed  Google Scholar 

  15. Mantovani A, Locati M, Vecchi A, Sozzani S, Allavena P (2001) Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol 22: 328–336

    Article  CAS  PubMed  Google Scholar 

  16. Bourke E, Cassetti A, Villa A, Fadlon E, Colotta F, Mantovani A (2003) IL-1beta scavenging by the Type II IL-1 decoy receptor in human neutrophils. J Immunol 170: 5999–6005

    CAS  PubMed  Google Scholar 

  17. Kobayashi K, Hernandez LD, Galan JE, Janeway CA Jr, Medzhitov R, Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110: 191–202

    Article  CAS  PubMed  Google Scholar 

  18. Burns K, Janssens S, Brissoni B, Olivos N, Beyaert R, Tschopp J (2003) Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J Exp Med 197: 263–268

    Article  PubMed  Google Scholar 

  19. Thomassen E, Renshaw BR, Sims JE (1999) Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine 11: 389–399

    Article  CAS  PubMed  Google Scholar 

  20. Polentarutti N, Penton Rol G, Muzio M, Zoja C, Benigni A, Tomasoni S, Vecchi A, Garlanda C, Mantovani A (2003) Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR. Eur Cytokine Netw 14: 1–8

    Google Scholar 

  21. Shortman K, Liu YJ (2002) Mouse and human dendritic cell subtypes. Nat Rev Immunol 2: 151–161

    Article  CAS  PubMed  Google Scholar 

  22. Garlanda C, Riva F, Polentarutti N, Buracchi C, Sironi M, De Bortoli M, Muzio M, Bergottini R, Scanziani E, Vecchi A et al (2004) Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc Natl Acad Sci USA 101: 3522–3526

    Article  CAS  PubMed  Google Scholar 

  23. Saccani S, Polentarutti N, Penton-Rol G, Sims JE, Mantovani A (1998) Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo. Cytokine 10: 773–780

    Article  CAS  PubMed  Google Scholar 

  24. Penton-Rol G, Orlando S, Polentarutti N, Bernasconi S, Muzio M, Introna M, Mantovani A (1999) Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts. J Immunol 162: 2931–2938

    CAS  PubMed  Google Scholar 

  25. Jensen LE, Muzio M, Mantovani A, Whitehead AS (2000) IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein. J Immunol 164: 5277–5286

    CAS  PubMed  Google Scholar 

  26. Muzio M, Ni J, Feng P, Dixit VM (1997) IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278: 1612–1615

    Article  CAS  PubMed  Google Scholar 

  27. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, Towne J, Sims JE, Stark GR, Li X (2003) SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 4: 920–927

    Article  CAS  PubMed  Google Scholar 

  28. Weshe H, Korherr C, Kracht M, Falk W, Resch K, Martin MU (1997) The interleukin-1 receptor accessory protein (IL-1RAcP) is essential for IL-1-induced activation of interleukin-1 receptor-associated kinase (IRAK) and stress-activated protein kinases (SAP kinases). J Biol Chem 272: 7727–7731

    Google Scholar 

  29. Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A (1998) The human Toll signaling pathway: divergence of NK-kB and JNK/SAPK activation upstream of TRAF6. J Exp Med 187: 2097–2101

    Article  CAS  PubMed  Google Scholar 

  30. O’Neill LA (2003) SIGIRR puts the brakes on Toll-like receptors. Nat Immunol 4: 823–824

    CAS  PubMed  Google Scholar 

  31. Vallet B, Wiel E (2001) Endothelial cell dysfunction and coagulation. Crit Care Med 29: S36–S41

    CAS  PubMed  Google Scholar 

  32. Froidevaux C, Roger T, Martin C, Glauser MP, Calandra T (2001) Macrophage migration inhibitory factor and innate immune responses to bacterial infections. Crit Care Med 29: S13–S15

    CAS  PubMed  Google Scholar 

  33. Suzuki A, Hanada T, Mitsuyama K, Yoshida T, Kamizono S, Hoshino T, Kubo M, Yamashita A, Okabe M, Takeda K et al (2001) CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J Exp Med 193: 471–481

    Article  CAS  PubMed  Google Scholar 

  34. Arai Y, Takanashi H, Kitagawa H, Okayasu I (1998) Involvement of interleukin-1 in the development of ulcerative colitis induced by dextran sulfate sodium in mice. Cytokine 10: 890–896

    Article  CAS  PubMed  Google Scholar 

  35. Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114: 385–391

    Article  CAS  PubMed  Google Scholar 

  36. Dinarello CA (2000) The role of the interleukin-1-receptor antagonist in blocking inflammation mediated by interleukin-1. N Engl J Med 343: 732–734

    Article  CAS  PubMed  Google Scholar 

  37. Siegmund B, Fantuzzi G, Rieder F, Gamboni-Robertson F, Lehr HA, Hartmann G, Dinarello CA, Endres S, Eigler A (2001) Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production. Am J Physiol Regul Integr Comp Physiol 281: R1264–R1273

    CAS  PubMed  Google Scholar 

  38. Ardizzone S, Porro GB (2002) Inflammatory bowel disease: new insights into pathogenesis and treatment. J Intern Med 252: 475–496

    Article  CAS  PubMed  Google Scholar 

  39. Bouma G, Strober W (2003) The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3: 521–533

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto Clinico Humanitas, via Manzoni 56, 20089, Rozzano, Italy

    Cecilia Garlanda, Alessia Cotena, Virginia Maina, Federica Moalli & Alberto Mantovani

  2. Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, via Scalzino 3, 62032, Camerino, Italy

    Michela Mosca

  3. Department of Animal Pathology, Faculty of Veterinary Medicine, University of Milan, via Celoria 10, 20133, Milan, Italy

    Federica Riva

  4. Centro di Eccellenza per l’Innovazione Diagnostica e Terapeutica (IDET) Institute of General Pathology, Faculty of Medicine, University of Milan, Via Mangiagalli 31, 20133, Milan, Italy

    Alberto Mantovani

Authors
  1. Cecilia Garlanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michela Mosca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessia Cotena
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Virginia Maina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Federica Moalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Federica Riva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alberto Mantovani
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Cytokine Research Group, Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland

    Luke A.J. O’Neill  & Elizabeth Brint  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Garlanda, C. et al. (2006). Tuning of inflammatory cytokines and toll-like receptors by TIR8/SIGIRR, a member of the IL-1 receptor family with unique structure and regulation. In: O’Neill, L.A., Brint, E. (eds) Toll-like Receptors in Inflammation. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7441-1_11

Download citation

Publish with us

Policies and ethics

Search

Navigation