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

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  • Amin Al-Shami
    1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
  • Rosanne Spolski
    1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
  • John Kelly
    1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
  • Andrea Keane-Myers
    2Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health Laboratory of Allergic Disease, Rockville, MD 20852
  • Warren J. Leonard
    1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892

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<jats:p>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-γ, 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.</jats:p>

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