کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2831563 1163809 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes
چکیده انگلیسی

T cell responses are determined by the environment in which antigen is encountered. In the absence of proper costimulation, anergizing stimuli induce the activation of a specific program of gene expression. Proteins encoded by these genes impose a state of functional unresponsiveness in anergic T cells through the activation of different mechanisms that include dampening of the T cell receptor signaling and direct inhibition of cytokine expression. Anergy can be reversed by stimulating T cells in the presence of interleukin (IL-)2. Signaling through the IL-2 receptor has been shown to activate mTOR, which plays an important role in the integration of signals that determine the fate of T cells. The mechanisms underlying the IL-2-dependent regulation of T cell tolerance are still not fully elucidated. In this study we show that IL-2 receptor signaling mediated through JAK3 and mTOR inhibits the expression of anergy-inducing genes independently of any effect on cell cycle progression. Interestingly, we also show that this effect is likely due to changes on the levels of AP-1 activation induced by IL-2 receptor signaling in T cells. Our data identifies a mechanism that can explain how IL-2 may prevent or reverse the establishment of anergy in T cells and, therefore, helps to understand how the cytokine environment can be determinant to shape the outcome of T cell responses – tolerance or activation – when antigen is encountered.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 46, Issue 5, February 2009, Pages 999–1006
نویسندگان
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