Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Jun 1;183(6):2593–2603. doi: 10.1084/jem.183.6.2593

T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines

PMCID: PMC2192621  PMID: 8676080

Abstract

Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning of human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony- stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.

Full Text

The Full Text of this article is available as a PDF (4.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahuja S. K., Murphy P. M. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J Biol Chem. 1993 Oct 5;268(28):20691–20694. [PubMed] [Google Scholar]
  2. Albrecht J. C., Nicholas J., Biller D., Cameron K. R., Biesinger B., Newman C., Wittmann S., Craxton M. A., Coleman H., Fleckenstein B. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. doi: 10.1128/jvi.66.8.5047-5058.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arai K. I., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. doi: 10.1146/annurev.bi.59.070190.004031. [DOI] [PubMed] [Google Scholar]
  4. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Coffman R. L., Seymour B. W., Hudak S., Jackson J., Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. doi: 10.1126/science.2787531. [DOI] [PubMed] [Google Scholar]
  7. Dale D. C., Liles W. C., Summer W. R., Nelson S. Review: granulocyte colony-stimulating factor--role and relationships in infectious diseases. J Infect Dis. 1995 Oct;172(4):1061–1075. doi: 10.1093/infdis/172.4.1061. [DOI] [PubMed] [Google Scholar]
  8. Dechanet J., Briolay J., Rissoan M. C., Chomarat P., Galizzi J. P., Banchereau J., Miossec P. IL-4 inhibits growth factor-stimulated rheumatoid synoviocyte proliferation by blocking the early phases of the cell cycle. J Immunol. 1993 Nov 1;151(9):4908–4917. [PubMed] [Google Scholar]
  9. Favre C., Saeland S., Caux C., Duvert V., De Vries J. E. Interleukin-4 has basophilic and eosinophilic cell growth-promoting activity on cord blood cells. Blood. 1990 Jan 1;75(1):67–73. [PubMed] [Google Scholar]
  10. Ferrara J. L., Michaelson J., Burakoff S. J., Mauch P. Engraftment following T cell-depleted bone marrow transplantation. III. Differential effects of increased total-body irradiation on semiallogeneic and allogeneic recipients. Transplantation. 1988 May;45(5):948–952. [PubMed] [Google Scholar]
  11. Gough N. M., Gough J., Metcalf D., Kelso A., Grail D., Nicola N. A., Burgess A. W., Dunn A. R. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. 1984 Jun 28-Jul 4Nature. 309(5971):763–767. doi: 10.1038/309763a0. [DOI] [PubMed] [Google Scholar]
  12. Hale G., Cobbold S., Waldmann H. T cell depletion with CAMPATH-1 in allogeneic bone marrow transplantation. Transplantation. 1988 Apr;45(4):753–759. doi: 10.1097/00007890-198804000-00018. [DOI] [PubMed] [Google Scholar]
  13. Hubbard A. L., Cohn Z. A. The enzymatic iodination of the red cell membrane. J Cell Biol. 1972 Nov;55(2):390–405. doi: 10.1083/jcb.55.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ikebuchi K., Wong G. G., Clark S. C., Ihle J. N., Hirai Y., Ogawa M. Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035–9039. doi: 10.1073/pnas.84.24.9035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jagels M. A., Hugli T. E. Neutrophil chemotactic factors promote leukocytosis. A common mechanism for cellular recruitment from bone marrow. J Immunol. 1992 Feb 15;148(4):1119–1128. [PubMed] [Google Scholar]
  16. Johnson K. J., Varani J., Smolen J. E. Neutrophil activation and function in health and disease. Immunol Ser. 1992;57:1–46. [PubMed] [Google Scholar]
  17. Kaushansky K., O'Hara P. J., Berkner K., Segal G. M., Hagen F. S., Adamson J. W. Genomic cloning, characterization, and multilineage growth-promoting activity of human granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 May;83(10):3101–3105. doi: 10.1073/pnas.83.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lieschke G. J., Burgess A. W. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (2). N Engl J Med. 1992 Jul 9;327(2):99–106. doi: 10.1056/NEJM199207093270207. [DOI] [PubMed] [Google Scholar]
  19. Metcalf D., Begley C. G., Johnson G. R., Nicola N. A., Lopez A. F., Williamson D. J. Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood. 1986 Jul;68(1):46–57. [PubMed] [Google Scholar]
  20. Metcalf D. Control of granulocytes and macrophages: molecular, cellular, and clinical aspects. Science. 1991 Oct 25;254(5031):529–533. doi: 10.1126/science.1948028. [DOI] [PubMed] [Google Scholar]
  21. Moore K. W., Vieira P., Fiorentino D. F., Trounstine M. L., Khan T. A., Mosmann T. R. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. doi: 10.1126/science.2161559. [DOI] [PubMed] [Google Scholar]
  22. Moreau I., Duvert V., Caux C., Galmiche M. C., Charbord P., Banchereau J., Saeland S. Myofibroblastic stromal cells isolated from human bone marrow induce the proliferation of both early myeloid and B-lymphoid cells. Blood. 1993 Oct 15;82(8):2396–2405. [PubMed] [Google Scholar]
  23. Paul W. E., Seder R. A. Lymphocyte responses and cytokines. Cell. 1994 Jan 28;76(2):241–251. doi: 10.1016/0092-8674(94)90332-8. [DOI] [PubMed] [Google Scholar]
  24. Peschel C., Paul W. E., Ohara J., Green I. Effects of B cell stimulatory factor-1/interleukin 4 on hematopoietic progenitor cells. Blood. 1987 Jul;70(1):254–263. [PubMed] [Google Scholar]
  25. Porath J., Carlsson J., Olsson I., Belfrage G. Metal chelate affinity chromatography, a new approach to protein fractionation. Nature. 1975 Dec 18;258(5536):598–599. doi: 10.1038/258598a0. [DOI] [PubMed] [Google Scholar]
  26. Rennick D., Yang G., Muller-Sieburg C., Smith C., Arai N., Takabe Y., Gemmell L. Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6889–6893. doi: 10.1073/pnas.84.19.6889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rouvier E., Luciani M. F., Mattéi M. G., Denizot F., Golstein P. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993 Jun 15;150(12):5445–5456. [PubMed] [Google Scholar]
  28. Saeland S., Caux C., Favre C., Aubry J. P., Mannoni P., Pebusque M. J., Gentilhomme O., Otsuka T., Yokota T., Arai N. Effects of recombinant human interleukin-3 on CD34-enriched normal hematopoietic progenitors and on myeloblastic leukemia cells. Blood. 1988 Nov;72(5):1580–1588. [PubMed] [Google Scholar]
  29. Sanderson C. J., Warren D. J., Strath M. Identification of a lymphokine that stimulates eosinophil differentiation in vitro. Its relationship to interleukin 3, and functional properties of eosinophils produced in cultures. J Exp Med. 1985 Jul 1;162(1):60–74. doi: 10.1084/jem.162.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schlager S. I. Radioiodination of cell surface lipids and proteins for use in immunological studies. Methods Enzymol. 1980;70(A):252–265. doi: 10.1016/s0076-6879(80)70054-x. [DOI] [PubMed] [Google Scholar]
  31. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  32. Ulich T. R., del Castillo J., Guo K. Z. In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood. 1989 Jan;73(1):108–110. [PubMed] [Google Scholar]
  33. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
  34. Yao Z., Painter S. L., Fanslow W. C., Ulrich D., Macduff B. M., Spriggs M. K., Armitage R. J. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995 Dec 15;155(12):5483–5486. [PubMed] [Google Scholar]
  35. Yokota T., Coffman R. L., Hagiwara H., Rennick D. M., Takebe Y., Yokota K., Gemmell L., Shrader B., Yang G., Meyerson P. Isolation and characterization of lymphokine cDNA clones encoding mouse and human IgA-enhancing factor and eosinophil colony-stimulating factor activities: relationship to interleukin 5. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7388–7392. doi: 10.1073/pnas.84.21.7388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES