• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. Jun 1, 1996; 183(6): 2593–2603.
PMCID: PMC2192621

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

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 (4.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Arai KI, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. [PubMed]
  • Paul WE, Seder RA. Lymphocyte responses and cytokines. Cell. 1994 Jan 28;76(2):241–251. [PubMed]
  • Rouvier E, Luciani MF, Mattéi MG, 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]
  • von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. [PubMed]
  • Dechanet J, Briolay J, Rissoan MC, Chomarat P, Galizzi JP, 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]
  • 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. [PubMed]
  • 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. [PubMed]
  • Hubbard AL, Cohn ZA. The enzymatic iodination of the red cell membrane. J Cell Biol. 1972 Nov;55(2):390–405. [PMC free article] [PubMed]
  • Schlager SI. Radioiodination of cell surface lipids and proteins for use in immunological studies. Methods Enzymol. 1980;70(A):252–265. [PubMed]
  • Saeland S, Caux C, Favre C, Aubry JP, Mannoni P, Pebusque MJ, Gentilhomme O, Otsuka T, Yokota T, Arai N, et al. 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]
  • Metcalf D. Control of granulocytes and macrophages: molecular, cellular, and clinical aspects. Science. 1991 Oct 25;254(5031):529–533. [PubMed]
  • Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (2). N Engl J Med. 1992 Jul 9;327(2):99–106. [PubMed]
  • Ulich TR, del Castillo J, Guo KZ. 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]
  • Ikebuchi K, Wong GG, Clark SC, Ihle JN, 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. [PMC free article] [PubMed]
  • Moreau I, Duvert V, Caux C, Galmiche MC, 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]
  • Ahuja SK, Murphy PM. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J Biol Chem. 1993 Oct 5;268(28):20691–20694. [PubMed]
  • Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG, et al. 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. [PubMed]
  • Metcalf D, Begley CG, Johnson GR, Nicola NA, Lopez AF, Williamson DJ. Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood. 1986 Jul;68(1):46–57. [PubMed]
  • Peschel C, Paul WE, 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]
  • 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. [PMC free article] [PubMed]
  • Favre C, Saeland S, Caux C, Duvert V, De Vries JE. Interleukin-4 has basophilic and eosinophilic cell growth-promoting activity on cord blood cells. Blood. 1990 Jan 1;75(1):67–73. [PubMed]
  • Yokota T, Coffman RL, Hagiwara H, Rennick DM, Takebe Y, Yokota K, Gemmell L, Shrader B, Yang G, Meyerson P, et al. 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. [PMC free article] [PubMed]
  • Coffman RL, Seymour BW, Hudak S, Jackson J, Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. [PubMed]
  • Sanderson CJ, Warren DJ, 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. [PMC free article] [PubMed]
  • Gough NM, Gough J, Metcalf D, Kelso A, Grail D, Nicola NA, Burgess AW, Dunn AR. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. Nature. 309(5971):763–767. [PubMed]
  • Kaushansky K, O'Hara PJ, Berkner K, Segal GM, Hagen FS, Adamson JW. 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. [PMC free article] [PubMed]
  • Jagels MA, Hugli TE. Neutrophil chemotactic factors promote leukocytosis. A common mechanism for cellular recruitment from bone marrow. J Immunol. 1992 Feb 15;148(4):1119–1128. [PubMed]
  • Dale DC, Liles WC, Summer WR, Nelson S. Review: granulocyte colony-stimulating factor--role and relationships in infectious diseases. J Infect Dis. 1995 Oct;172(4):1061–1075. [PubMed]
  • Johnson KJ, Varani J, Smolen JE. Neutrophil activation and function in health and disease. Immunol Ser. 1992;57:1–46. [PubMed]
  • Hale G, Cobbold S, Waldmann H. T cell depletion with CAMPATH-1 in allogeneic bone marrow transplantation. Transplantation. 1988 Apr;45(4):753–759. [PubMed]
  • Ferrara JL, Michaelson J, Burakoff SJ, 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]
  • Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK, Armitage RJ. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995 Dec 15;155(12):5483–5486. [PubMed]
  • Albrecht JC, Nicholas J, Biller D, Cameron KR, Biesinger B, Newman C, Wittmann S, Craxton MA, Coleman H, Fleckenstein B, et al. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. [PMC free article] [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...