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,§
*
Virginia Mason Research Center, Seattle, WA 98101;
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263; and Departments of
Immunology and
§
Biological Structure, University of Washington, Seattle, WA 98195
Thymic stromal lymphopoietin (TSLP) is a newly identified cytokine
that uniquely promotes B lymphopoiesis to the
B220+/IgM+ immature B cell stage. In addition,
TSLP shares many biological properties with the related cytokine IL-7.
This can be explained by the finding that the receptor complexes for
TSLP and IL-7 both contain the IL-7R 
-chain; IL-7R is paired with
the common 
-chain (c) in the IL-7 receptor complex and the unique
TSLP-R chain in the TSLP receptor complex. Although TSLP and IL-7 both
induce tyrosine phosphorylation of the transcription factor Stat5, only
IL-7-mediated signal transduction could be associated with activation
of Janus family kinases (Jaks). Because Stat5 phosphorylation following
cytokine stimulation is generally mediated by Jaks, the lack of Jak
activation after TSLP treatment suggested the possibility that
tyrosine-phosphorylated Stat5 may be nonfunctional. Herein, we
demonstrate that TSLP induces a functional Stat5 transcription factor
in that TSLP stimulation results in Stat5-DNA complex formation and
transcription of the Stat5-responsive gene CIS. We also show that the
TSLP receptor complex is functionally reconstituted using TSLP-R and
IL-7R and that TSLP-mediated signal transduction requires Stat5.
Moreover, TSLP-mediated signaling is inhibited by suppressor of
cytokine signaling (SOCS)-1 and a kinase-deficient version of Tec but
not by kinase-deficient forms of Jak1 and Jak2.
This article has been cited by other articles:
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Y. Torii, T. Ito, R. Amakawa, H. Sugimoto, H. Amuro, T. Tanijiri, Y. Katashiba, M. Ogata, T. Yokoi, and S. Fukuhara Imidazoquinoline Acts as Immune Adjuvant for Functional Alteration of Thymic Stromal Lymphopoietin-Mediated Allergic T Cell Response J. Immunol., October 15, 2008; 181(8): 5340 - 5349. [Abstract] [Full Text] [PDF]
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 S. Chappaz, L. Flueck, A. G. Farr, A. G. Rolink, and D. Finke Increased TSLP availability restores T- and B-cell compartments in adult IL-7 deficient mice Blood, December 1, 2007; 110(12): 3862 - 3870. [Abstract] [Full Text] [PDF]
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 C. A. J. Vosshenrich, A. Cumano, W. Muller, J. P. Di Santo, and P. Vieira Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment PNAS, July 27, 2004; 101(30): 11070 - 11075. [Abstract] [Full Text] [PDF]
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 N. Carpino, W. E. Thierfelder, M.-s. Chang, C. Saris, S. J. Turner, S. F. Ziegler, and J. N. Ihle Absence of an Essential Role for Thymic Stromal Lymphopoietin Receptor in Murine B-Cell Development Mol. Cell. Biol., March 15, 2004; 24(6): 2584 - 2592. [Abstract] [Full Text] [PDF]
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M. J. Osborn, P. L. Ryan, N. Kirchhof, A. Panoskaltsis-Mortari, F. Mortari, and K.-S. R. S. Tudor Overexpression of murine TSLP impairs lymphopoiesis and myelopoiesis Blood, February 1, 2004; 103(3): 843 - 851. [Abstract] [Full Text] [PDF]
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D. E. Isaksen, H. Baumann, B. Zhou, S. Nivollet, A. G. Farr, S. D. Levin, and S. F. Ziegler Uncoupling of Proliferation and Stat5 Activation in Thymic Stromal Lymphopoietin-Mediated Signal Transduction J. Immunol., April 1, 2002; 168(7): 3288 - 3294. [Abstract] [Full Text] [PDF]
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 C. J. Greenhalgh and D. J. Hilton Negative regulation of cytokine signaling J. Leukoc. Biol., September 1, 2001; 70(3): 348 - 356. [Abstract] [Full Text] [PDF]
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 D. L. Krebs and D. J. Hilton SOCS Proteins: Negative Regulators of Cytokine Signaling Stem Cells, September 1, 2001; 19(5): 378 - 387. [Abstract] [Full Text] [PDF]
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P. A. Reche, V. Soumelis, D. M. Gorman, T. Clifford, M.-r. Liu, M. Travis, S. M. Zurawski, J. Johnston, Y.-J. Liu, H. Spits, et al. Human Thymic Stromal Lymphopoietin Preferentially Stimulates Myeloid Cells J. Immunol., July 1, 2001; 167(1): 336 - 343. [Abstract] [Full Text] [PDF]
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K. J. Hare, E. J. Jenkinson, and G. Anderson An Essential Role for the IL-7 Receptor During Intrathymic Expansion of the Positively Selected Neonatal T Cell Repertoire J. Immunol., September 1, 2000; 165(5): 2410 - 2414. [Abstract] [Full Text] [PDF]
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 D. Krebs and D. Hilton SOCS: physiological suppressors of cytokine signaling J. Cell Sci., January 8, 2000; 113(16): 2813 - 2819. [Abstract] [PDF]
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