Skip to main content
SpringerLink
Log in
Book cover

Advances in TNF Family Research pp 375–382Cite as

Involvement of the Cytokine Receptor CD137 in Murine Hematopoiesis

  • Conference paper
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 691))

Abstract

CD137 and CD137 ligand are members of the tumor necrosis factor (TNF) receptor and TNF family, respectively. CD137 is expressed by cells in the bone marrow and CD137 ligand is expressed on hematopoietic progenitor cells. The interaction of CD137 and CD137 ligand induced proliferation and colony formation of hematopoietic progenitor cells and their differentiation to macrophages. Since CD137 is expressed on activated immune cells the CD137-induced myelopoiesis may take place during ongoing immune responses. However, in a steady-state condition the CD137 receptor/ligand system seems to inhibit myelopoiesis. Current data only indicate an involvement of CD137 and its ligand in myelopoiesis while other hematopoietic lineages are not affected.

This is a preview of subscription content, 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   259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
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

Learn about institutional subscriptions

References

  1. Broll K, Richter G, Pauly S, Hofstaedter F, Schwarz H (2001) CD137 expression in tumor vessel walls. High correlation with malignant tumors. Am J Clin Pathol 115:543–549

    Article  CAS  PubMed  Google Scholar 

  2. Choi BK, Kim HY, Kwon MP, Lee CS, Kang WS, Kim SM, Lee JM, and Kwon SB (2009) 4-1BB functions as a survival factor in dendritic cells. J Immunol 182:4107–4115

    Article  CAS  PubMed  Google Scholar 

  3. Coutinho LM, Gilleece HM, de Wynter EA, Will A, Testa GN (1993) Hematopoiesis: a practical approach. In Testa GN, Molineux G (eds). Oxford University Press, New York, 75–106

    Google Scholar 

  4. Croft M (2003) Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol 3:609–620

    Article  CAS  PubMed  Google Scholar 

  5. Drenkard D, Becke FM, Langstein J, Spruss T, Kunz-Schughart AL, Tan TE, Lim CY, Schwarz H (2007) CD137 is expressed on blood vessel walls at sites of inflammation and enhances monocyte migratory activity. FASEB J 21:456–463

    Article  CAS  PubMed  Google Scholar 

  6. Eissner G, Kolch W, Scheurich P (2004) Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system. Cytokine Growth Factor Rev 15:353–366

    Article  CAS  PubMed  Google Scholar 

  7. Hong HJ, Lee JW, Park SS, Kang YJ, Chang SY, Kim KM, Kim JO, Murthy KK, Payne JS, Yoon SK, Park MJ, Kim IC, Kim JG, Kang CY (2000). A humanized anti-4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates. J Immunother 23:613–621

    Article  CAS  PubMed  Google Scholar 

  8. Jiang D, Chen Y, Schwarz H (2008) CD137 induces proliferation of murine hematopoietic progenitor cells and differentiation to macrophages. J Immunol 181:3923–3932

    CAS  PubMed  Google Scholar 

  9. Kang YJ, Kim SO, Shimada S, Otsuka M, Seit-Nebi A, Kwon SB, Watts TH, Han J (2007) Cell surface 4-1BBL mediates sequential signaling pathways ‘downstream’ of TLR and is required for sustained TNF production in macrophages. Nat Immunol 8:601–609

    Article  CAS  PubMed  Google Scholar 

  10. Kim YJ, Li G, Broxmeyer HE (2002) 4-1BB ligand stimulation enhances myeloid dendritic cell maturation from human umbilical cord blood CD34+ progenitor cells. J Hematother Stem Cell Res 11:895–903

    Article  CAS  PubMed  Google Scholar 

  11. Kwon BS, Weissman SM (1989) cDNA sequences of two inducible T-cell genes. Proc Natl Acad Sci U S A 86:1963–1967

    Article  CAS  PubMed  Google Scholar 

  12. Kwon BS, Hurtado JC, Lee ZH, Kwack KB, Seo SK, Choi BK, Koller BH, Wolisi G, Broxmeyer HE, Vinay DS (2002) Immune responses in 4-1BB (CD137)-deficient mice. J Immunol 168:5483–5490

    CAS  PubMed  Google Scholar 

  13. Laderach D, Wesa A, Galy A (2003) 4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12. Cell Immunol 226:37–44

    Article  CAS  PubMed  Google Scholar 

  14. Langstein J, Michel J, Fritsche J, Kreutz M, Andreesen R, Schwarz H (1998) CD137 (ILA/4-1BB), a member of the TNF receptor family, induces monocyte activation via bidirectional signaling. J Immunol 160:2488–2494

    CAS  PubMed  Google Scholar 

  15. Langstein J, Schwarz H (1999) Identification of CD137 as a potent monocyte survival factor. J Leukoc Biol 65:829–833

    CAS  PubMed  Google Scholar 

  16. Langstein J, Michel J, Schwarz H (1999) CD137 induces proliferation and endomitosis in monocytes. Blood 94:3161–3168

    CAS  PubMed  Google Scholar 

  17. Langstein J, Becke FM, Sollner L, Krause G, Brockhoff G, Kreutz M, Andreesen R, Schwarz H (2000) Comparative analysis of CD137 and LPS effects on monocyte activation, survival, and proliferation. Biochem Biophys Res Commun 273:117–122

    Article  CAS  PubMed  Google Scholar 

  18. Lee SW, Park Y, So T, Kwon BS, Cheroutre H, Mittler RS, Croft M (2008) Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells. Nat Immunol 9:917–926

    Article  CAS  PubMed  Google Scholar 

  19. Lippert U, Zachmann K, Ferrari DM, Schwarz H, Brunner E, Latif AH, Neumann C, Soruri A (2008) CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response. Eur J Immunol 38:1024–1032

    Article  CAS  PubMed  Google Scholar 

  20. Melero I, Johnston JV, Shufford WW, Mittler RS, Chen L (1998) NK1.1 cells express 4-1BB (CDw137) costimulatory molecule and are required for tumor immunity elicited by anti-4-1BB monoclonal antibodies. Cell Immunol 15;190(2):167–72

    Article  Google Scholar 

  21. Niu L, Strahotin S, Hewes B, Zhang B, Zhang Y, Archer D, Spencer T, Dillehay D, Kwon B, Chen L, Vella TA, Mittler RS (2007) Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice. J Immunol 178:4194–4213

    CAS  PubMed  Google Scholar 

  22. Olofsson PS, Soderstrom LA, Wagsater D, Sheikine Y, Ocaya P, Lang F, Rabu C, Chen L, Rudling M, Aukrust P, Hedin U, Paulsson-Berne G, Sirsjo A, Hansson GK (2008) CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation 117:1292–1301

    Article  CAS  PubMed  Google Scholar 

  23. Saito K, Ohara N, Hotokezaka H, Fukumoto S, Yuasa K, Naito M, Fujiwara T, Nakayama K (2004) Infection-induced up-regulation of the costimulatory molecule 4-1BB in osteoblastic cells and its inhibitory effect on M-CSF/RANKL-induced in vitro osteoclastogenesis. J Biol Chem 279:13555–13563

    Article  CAS  PubMed  Google Scholar 

  24. Schwarz H, Tuckwell J, Lotz M (1993) A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family. Gene 134:295–298

    Article  CAS  PubMed  Google Scholar 

  25. Schwarz H, Valbracht J, Tuckwell J, J. von Kempis, Lotz M (1995) ILA, the human 4-1BB homologue, is inducible in lymphoid and other cell lineages. Blood 85:1043–1052

    CAS  PubMed  Google Scholar 

  26. Schwarz H (2005) Biological activities of reverse signal transduction through CD137 ligand. J Leukoc Biol 77:281–286

    CAS  PubMed  Google Scholar 

  27. Shin HH, Lee EA, Kim SJ, Kwon BS, Choi HS (2006) A signal through 4-1BB ligand inhibits receptor for activation of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis by increasing interferon (IFN)-beta production. FEBS Lett 580:1601–1606

    Article  CAS  PubMed  Google Scholar 

  28. Sica G, Chen L (2000) Modulation of the immune response through 4-1BB. Adv Exp Med Biol 465:355–362

    Article  CAS  PubMed  Google Scholar 

  29. Son JH, Lee UG, Lee JJ, Kwon B, Kwon BS, Park JW (2004) Humanization of agonistic anti-human 4-1BB monoclonal antibody using a phage-displayed combinatorial library. J Immunol Methods 286:187–201

    Article  CAS  PubMed  Google Scholar 

  30. Watts TH (2005) TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 23:23–68

    Article  CAS  PubMed  Google Scholar 

  31. Yoon D, Pastore YD, Divoky V, Liu E, Mlodnicka AE, Rainey K, Ponka P, Semenza GL, Schumacher A, Prchal JT (2006) Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem 281:25703–25711

    Article  CAS  PubMed  Google Scholar 

  32. Zhu G, Flies DB, Tamada K, Sun Y, Rodriguez M, Fu YX, Chen L (2001) Progressive depletion of peripheral B lymphocytes in 4-1BB (CD137) ligand/I-Ealpha)-transgenic mice. J Immunol 167:2671–2676

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Part of this chapter is based on Jiang et al. [8]. Copyright 2008. The American Association of Immunologists, Inc.

Author information

Authors and Affiliations

  1. Department of Physiology and Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, Singapore, Singapore, 117597

    Dongsheng Jiang, Qianqiao Tang & Herbert Schwarz

Authors
  1. Dongsheng Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qianqiao Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Herbert Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Herbert Schwarz .

Editor information

Editors and Affiliations

  1. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    David Wallach

  2. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    Andrew Kovalenko

  3. Kennedy Institute of Rheumatology, Imperial College London, Aspenlea Rd. 1, London, W6 8LH, United Kingdom

    Marc Feldmann

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this paper

Cite this paper

Jiang, D., Tang, Q., Schwarz, H. (2011). Involvement of the Cytokine Receptor CD137 in Murine Hematopoiesis. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_38

Download citation

Publish with us

Policies and ethics

Search

Navigation