Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta

Abstract

The cytokine receptor family type 2 (CRF2) comprises receptors for important immunomediators like interferons and interleukin-10 (IL-10). We identified a novel member of this family which represents the first exclusively soluble receptor in this group and was therefore designated as CRF2-soluble 1 (CRF2-s1). The CRF2-s1 gene covers about 28 kb and is located on chromosome 6 in close proximity to the CRF2 members interferon (IFN)-γ receptor 1 and IL-20 receptor 1. It comprises seven exons and generates two different mRNA splice variants, CRF2-s1-long and CRF2-s1-short. CRF2-s1-long and CRF2-s1-short encode proteins of 263 and 231 amino acids, respectively. A comparison of predicted protein structures led to the postulation that each receptor variants binds a different ligand. Quantitative analysis of human mRNA expression revealed a very restricted pattern for both splice forms. CRF2-s1 turned out to be the first member of this receptor family which was expressed neither in resting nor in stimulated leucocyte populations. CRF2-s1-long was only expressed in placenta, whereas CRF2-s1-short was additionally expressed in human mammary gland and, at a lower level, in skin, spleen, thymus and stomach. The preferential expression of CRF2-s1 in placenta suggests a role for this receptor in establishing and maintaining successful pregnancy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gallagher G, Dickensheets H, Eskdale J et al Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10) Genes Immun 2000 1 442–450

    Article  CAS  PubMed  Google Scholar 

  2. Blumberg H, Conklin D, Xu WF et al Interleukin 20: discovery, receptor identification, and role in epidermal function Cell 2001 104 9–19

    Article  CAS  PubMed  Google Scholar 

  3. Dumoutier L, Louahed J, Renauld JC Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9 J Immunol 2000 164 1814–1819

    Article  CAS  PubMed  Google Scholar 

  4. Knappe A, Hor S, Wittmann S, Fickenscher H Induction of a novel cellular homolog of interleukin-10, AK155, by transformation of T lymphocytes with herpesvirus saimiri J Virol 2000 74 3881–3887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jiang H, Lin JJ, Su ZZ, Goldstein NI, Fisher PB Subtraction hybridization identifies a novel melanoma differentiation associated gene, MDA-7, modulated during human melanoma differentiation, growth and progression Oncogene 1995 11 2477–2486

    CAS  PubMed  Google Scholar 

  6. Dumoutier L, Van Roost E, Ameye G, Michaux L, Renauld JC IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes Genes Immun 2000 1 488–494

    Article  CAS  PubMed  Google Scholar 

  7. Kotenko SV, Pestka S Jak-Stat signal transduction pathway through the eyes of cytokine class II receptor complexes Oncogene 2000 19 2557–2565

    Article  CAS  PubMed  Google Scholar 

  8. Bazan JF Structural design and molecular evolution of a cytokine receptor superfamily Proc Natl Acad Sci USA 1990 87 6934–6938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW A receptor for interleukin 10 is related to interferon receptors Proc Natl Acad Sci USA 1993 90 11267–11271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S Identification and functional characterization of a second chain of the interleukin-10 receptor complex EMBO 1997 16 5894–5903

    Article  CAS  Google Scholar 

  11. 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 1079–1090

    CAS  PubMed  Google Scholar 

  12. Dumoutier L, Van Roost E, Colau D, Renauld JC Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor Proc Natl Acad Sci USA 2000 97 10144–10149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xie MH, Aggarwal S, Ho WH et al Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2–4 and IL-22R J Biol Chem 2000 275 31335–31339

    Article  CAS  PubMed  Google Scholar 

  14. Kotenko SV, Izotova LS, Mirochnitchenko OV et al Identification of the functional IL-TIF (IL-22) receptor complex: the IL-10R2 chain (IL-10Rβ) is a shared component of both IL-10 and IL-TIF (IL-22) receptor complexes J Biol Chem 2001 276 2725–2732

    Article  CAS  PubMed  Google Scholar 

  15. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A Interleukin-10 and the interleukin-10 receptor Annu Rev Immunol 2001 19 683–765

    Article  CAS  PubMed  Google Scholar 

  16. Jiang H, Su ZZ, Lin JJ, Goldstein NI, Young CS, Fisher PB The melanoma differentiation associated gene MDA-7 suppresses cancer cell growth Proc Natl Acad Sci USA 1996 93 9160–9165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Su ZZ, Madireddi MT, Lin JJ et al The cancer growth suppressor gene MDA-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice Proc Natl Acad Sci USA 1998 95 14400–14405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nielsen H, Engelbrecht J, Brunak S, von Heijne G Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites Protein Eng 1997 10 1–6

    Article  CAS  PubMed  Google Scholar 

  19. Hershey GK, Schreiber RD Biosynthetic analysis of the human interferon-gamma receptor. Identification of N-linked glycosylation intermediates J Biol Chem 1989 264 11981–11988

    CAS  PubMed  Google Scholar 

  20. Hoover DM, Schalk-Hihi C, Chou CC, Menon S, Wlodawer A, Zdanov A Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization Eur J Biochem 1999 262 134–141

    Article  CAS  PubMed  Google Scholar 

  21. Dumoutier L, Lejeune D, Colau D, Renauld JC Cloning and characterization of Interleukin-22 Binding Protein (IL-22BP), a natural antagonist of IL-TIF/IL-22 J Immunol 2001 166 7090–7095

    Article  CAS  PubMed  Google Scholar 

  22. Kotenko SV, Izotova LS, Mirochnitchenko Ov et al Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity J Immunol 2001 166 7096–7103

    Article  CAS  PubMed  Google Scholar 

  23. Fernandez-Botran R, Chilton PM, Ma Y Soluble cytokine receptors: Their roles in immunoregulation, disease, and therapy Adv Immunol 1996 63 269–336

    Article  CAS  PubMed  Google Scholar 

  24. Heaney ML, Golde DW Soluble receptors in human disease J Leukoc Biol 1998 64 135–146

    Article  CAS  PubMed  Google Scholar 

  25. Dinarello CA Biologic basis for interleukin-1 in disease Blood 1996 87 2095–2147

    CAS  PubMed  Google Scholar 

  26. Dinarello CA Cytokines as endogenous pyrogens J Infect Dis 1999 179 (Suppl 2) 294–304

    Article  Google Scholar 

  27. Mohler KM, Torrance DS, Smith CA et al Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists J Immunol 1993 151 1548–1561

    CAS  PubMed  Google Scholar 

  28. Raghupathy R Th1-type immunity is incompatible with successful pregnancy Immunol Today 1997 18 478–482

    Article  CAS  PubMed  Google Scholar 

  29. Mellor AL, Munn DH Immunology at the maternal-fetal interface: lessons for T cell tolerance and suppression Annu Rev Immunol 2000 18 367–391

    Article  CAS  PubMed  Google Scholar 

  30. Walter MR, Windsor WT, Nagabhushan TL et al Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor Nature 1995 376 230–235

    Article  CAS  PubMed  Google Scholar 

  31. Zdanov A, Schalk-Hihi C, Wlodawer A Crystal structure of human interleukin-10 at 1.6 A resolution and a model of a complex with its soluble receptor Protein Sci 1996 5 1955–1962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Reineke U, Sabat R, Volk HD, Schneider-Mergener J Mapping of the interleukin-10/interleukin-10 receptor combining site Protein Sci 1998 7 951–960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wolk K, Döcke W-D, von Baehr V, Volk H-D, Sabat R Impaired antigen presentation by human monocytes during endotoxin tolerance Blood 2000 96 218–223

    CAS  PubMed  Google Scholar 

  34. Asadullah K, Friedrich M, Hanneken S et al Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings J Invest Dermatol 2001 116 721–727

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Antje Häussler-Quade, Ricardo Wieseke and Sabine Zeinert for excellent technical help. Special thanks is due to Prof H-D Volk, Prof P Donner, Dr W-D Döcke and Dr C Höflich (Berlin) for critical reading and commenting the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Sabat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gruenberg, B., Schoenemeyer, A., Weiss, B. et al. A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta. Genes Immun 2, 329–334 (2001). https://doi.org/10.1038/sj.gene.6363786

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363786

Keywords

This article is cited by

Search

Quick links