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Published 19 September 2005. doi:10.1084/jem.20050199
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 6, 829-839
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ARTICLE

 A role for TSLP in the development of inflammation in an asthma model

Amin Al-Shami1, Rosanne Spolski1, John Kelly1, Andrea Keane-Myers2, and Warren J. Leonard1

1 Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
2 Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health Laboratory of Allergic Disease, Rockville, MD 20852

CORRESPONDENCE Warren J. Leonard: wjl{at}helix.nih.gov

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.

Abbreviations used: {gamma}c, receptor {gamma} chain; ALUM, aluminum hydroxide; BAL, bronchoalveolar lavage; CFSE, 5,6-carboxyfluorescein diacetate-succinimidyl ester; IL-7R{alpha}, IL-7 receptor {alpha} chain; i.n., intranasal; i.t., intratracheal; Tg, transgenic; TSLP, thymic stromal lymphopoietin.


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