Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 24, Issue 6, Pages 2584-2592Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.6.2584-2592.2004
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Funding
- NCI NIH HHS [CA21765, 5-F32-CA83269, P30 CA021765, F32 CA083269] Funding Source: Medline
- NHLBI NIH HHS [P01 HL53749, P01 HL053749] Funding Source: Medline
- NIAID NIH HHS [R01 AI044259, R01 AI44259] Funding Source: Medline
- NIDDK NIH HHS [R01 DK042932, R01 DK42932] Funding Source: Medline
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The murine cytokine thymic stromal lymphopoietin (TSLP) supports the development of B220(+) IgM(+) immature B cells and induces thymocyte proliferation in vitro. Human TSLP, by contrast, activates CD11c(+) dendritic cells, but not B or T cells. Recent studies have demonstrated that the receptor for TSLP consists of a heterodimer of the interleukin 7 (IL-7) alpha chain and a novel protein that resembles the hematopoietic cytokine receptor common gamma chain. We examined signal transduction by the gamma-like chains using chimeric receptor proteins. The cytoplasmic domain of the human, but not of the murine, gamma-like chain, activates Jak2 and Stat5 and supports the proliferation of hematopoietic cell lines. In order to assess the role of the murine gamma-like chain in vivo, we generated gamma-like chain-deficient mice. Receptor-deficient mice are unresponsive to TSLP but exhibit no obvious phenotypic defects. In particular, hematopoietic cell development appeared normal. B-cell development, including the IgM(+) compartment, was unaffected by loss of the TSLP pathway, as were T lymphopoiesis and lymphocyte proliferation in vitro. Cytokine receptors that utilize the common gamma chain signal through the lymphocyte-specific kinase Jak3. Mice deficient in Jak3 exhibit a SCID phenotype but harbor a residual B220(+) splenic lymphocyte population. We demonstrate here that this residual lymphocyte population is lost in mice lacking both the gamma-like chain and Jak3.
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