Cutting Edge: Direct Action of Thymic Stromal Lymphopoietin on Activated Human CD4+ T Cells
Tóm tắt
Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis and contributes to allergic and inflammatory responses. TSLP can act directly on mouse CD4+ T cells, but in humans, the available data have indicated that TSLP receptors are not expressed on CD4+ T cells and that TSLP instead activates dendritic cells, which in turn promote the proliferation and differentiation of CD4+ T cells. We now unexpectedly demonstrate the presence of TSLP receptors on activated human CD4+ T cells. Strikingly, whereas freshly isolated peripheral blood human T cells show little if any response to TSLP, TCR stimulation allows a potent response to this cytokine. Moreover, TSLP increases the sensitivity of human CD4+ T cells to low doses of IL-2, augmenting responsiveness of these cells to TCR engagement. Our results establish that human CD4+ T cells are direct targets for TSLP.
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Tài liệu tham khảo
Friend, S. L., S. Hosier, A. Nelson, D. Foxworthe, D. E. Williams, A. Farr. 1994. A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp. Hematol. 22: 321-328.
Namen, A. E., S. Lupton, K. Hjerrild, J. Wignall, D.Y. Mochizuki, A. Schmierer, B. Mosley, C. J. March, D. Urdal, S. Gillis. 1988. Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 333: 571-573.
Pandey, A., K. Ozaki, H. Baumann, S. D. Levin, A. Puel, A. G. Farr, S. F. Ziegler, W. J. Leonard, H. F. Lodish. 2000. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat. Immunol. 1: 59-64.
Park, L. S., U. Martin, K. Garka, B. Gliniak, J. P. Di Santo, W. Muller, D. A. Largaespada, N. G. Copeland, N. A. Jenkins, A. G. Farr, et al 2000. Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J. Exp. Med. 192: 659-670.
Noguchi, M., H. Yi, H. M. Rosenblatt, A. H. Filipovich, S. Adelstein, W. S. Modi, O. W. McBride, W. J. Leonard. 1993. Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73: 147-157.
von Freeden-Jeffry, U., P. Vieira, L. A. Lucian, T. McNeil, S. E. Burdach, R. Murray. 1995. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181: 1519-1526.
Peschon, J. J., P. J. Morrissey, K. H. Grabstein, F. J. Ramsdell, E. Maraskovsky, B. C. Gliniak, L. S. Park, S. F. Ziegler, D. E. Williams, C. B. Ware, et al 1994. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180: 1955-1960.
Puel, A., S. F. Ziegler, R. H. Buckley, W. J. Leonard. 1998. Defective IL7R expression in T−B+NK+ severe combined immunodeficiency. Nat. Genet. 20: 394-397.
Al-Shami, A., R. Spolski, J. Kelly, T. Fry, P. L. Schwartzberg, A. Pandey, C. L. Mackall, W. J. Leonard. 2004. A role for thymic stromal lymphopoietin in CD4+ T cell development. J. Exp. Med. 200: 159-168.
Al-Shami, A., R. Spolski, J. Kelly, A. Keane-Myers, W. J. Leonard. 2005. A role for TSLP in the development of inflammation in an asthma model. J. Exp. Med. 202: 829-839.
Zhou, B., M. R. Comeau, T. De Smedt, H. D. Liggitt, M. E. Dahl, D. B. Lewis, D. Gyarmati, T. Aye, D. J. Campbell, S. F. Ziegler. 2005. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat. Immunol. 6: 1047-1053.
Yoo, J., M. Omori, D. Gyarmati, B. Zhou, T. Aye, A. Brewer, M. R. Comeau, D. J. Campbell, S. F. Ziegler. 2005. Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J. Exp. Med. 202: 541-549.
Ying, S., B. O’Connor, J. Ratoff, Q. Meng, K. Mallett, D. Cousins, D. Robinson, G. Zhang, J. Zhao, T. H. Lee, C. Corrigan. 2005. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 174: 8183-8190.
Ziegler, S. F., Y. J. Liu. 2006. Thymic stromal lymphopoietin in normal and pathogenic T cell development and function. Nat. Immunol. 7: 709-714.
Reche, P. A., V. Soumelis, D. M. Gorman, T. Clifford, M. Liu, M. Travis, S. M. Zurawski, J. Johnston, Y. J. Liu, H. Spits, et al 2001. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J. Immunol. 167: 336-343.
Isaksen, D. E., H. Baumann, P. A. Trobridge, A. G. Farr, S. D. Levin, S. F. Ziegler. 1999. Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction. J. Immunol. 163: 5971-5977.
John, S., C. M. Robbins, W. J. Leonard. 1996. An IL-2 response element in the human IL-2 receptor α chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein. EMBO J. 15: 5627-5635.
Kim, H. P., J. Kelly, W. J. Leonard. 2001. The basis for IL-2-induced IL-2 receptor α chain gene regulation: importance of two widely separated IL-2 response elements. Immunity 15: 159-172.
Matsumoto, A., M. Masuhara, K. Mitsui, M. Yokouchi, M. Ohtsubo, H. Misawa, A. Miyajima, A. Yoshimura. 1997. CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation. Blood 89: 3148-3154.
Sharon, M., R. D. Klausner, B. R. Cullen, R. Chizzonite, W. J. Leonard. 1986. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science 234: 859-863.
Kim, H. P., J. Imbert, W. J. Leonard. 2006. Both integrated and differential regulation of components of the IL-2/IL-2 receptor system. Cytokine Growth Factor Rev. 17: 349-366.
Puel, A., W. J. Leonard. 2000. Mutations in the gene for the IL-7 receptor result in T−B+NK+ severe combined immunodeficiency disease. Curr. Opin. Immunol. 12: 468-473.