A Role for TSLP in the Development of Inflammation in an Asthma Model

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Sep 21

PMID 16172260

Citations 240

Authors

Amin Al-Shami

Rosanne Spolski

John Kelly

Andrea Keane-Myers

Warren J Leonard

Affiliations

Soon will be listed here.

Abstract

Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis. We now demonstrate that TSLP is required to mount a normal CD4+ T cell-mediated inflammatory response. TSLP acts directly on naive, but not, memory CD4+ T cells, and promotes their proliferation in response to antigen. In addition, TSLP exerts an effect indirectly through DCs to promote Th2 differentiation of CD4+ T cells. Correspondingly, TSLP receptor (TSLPR) knockout (KO) mice exhibit strong Th1 responses, with high levels of interleukin (IL)-12, interferon-gamma, and immunoglobulin (Ig) G2a, but low production of IL-4, -5, -10, -13, and IgE; moreover, CD4+ T cells from these animals proliferate less well in response to antigen. Furthermore, TSLPR KO mice fail to develop an inflammatory lung response to inhaled antigen unless supplemented with wild-type CD4+ T cells. This underscores an important role for this cytokine in the development of inflammatory and/or allergic responses in vivo.

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