Absence of an Essential Role for Thymic Stromal Lymphopoietin Receptor in Murine B-Cell Development

Nick Carpino, William E. Thierfelder, Ming Shi Chang, Chris Saris, Steven J. Turner, Steven F. Ziegler, James N. Ihle

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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) α chain and a novel protein that resembles the hematopoietic cytokine receptor common γ chain. We examined signal transduction by the γ-like chains using chimeric receptor proteins. The cytoplasmic domain of the human, but not of the murine, γ-like chain, activates Jak2 and Stat5 and supports the proliferation of hematopoietic cell lines. In order to assess the role of the murine γ-like chain in vivo, we generated γ-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 γ 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 γ-like chain and Jak3.

Original languageEnglish
Pages (from-to)2584-2592
Number of pages9
JournalMolecular and Cellular Biology
Volume24
Issue number6
DOIs
Publication statusPublished - 2004 Mar 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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