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• W2967507951 abstract "The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP -/- ) interferes with T cell activation and polarization. Polyclonally stimulated KSRP -/- CD4 + T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells. In supernatants of stimulated KSRP -/- CD4 + T cells, levels of IL-5, IL-9, IL-10, and IL-13 were observed to be increased compared to those of the control group. KSRP -/- CD8 + T cells showed no altered proliferative capacity upon polyclonal stimulation, but supernatants contained lower levels of interferon- γ . Similar changes in the cytokine expression patterns were also detected in T cells derived from KSRP -/- mice undergoing arthritis induction indicative of a pathophysiological role of KSRP-dependent T cell polarization. We demonstrated the direct binding of KSRP to the 3<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:msup><mml:mrow /><mml:mrow><mml:mo>′</mml:mo></mml:mrow></mml:msup></mml:math>untranslated region of IL-13, IL-10, and IFN- γ mRNA in in vitro experiments. Moreover, since IL-4 mRNA decay was reduced in KSRP -/- CD4 + T cells, we identify KSRP as a negative regulator of IL-4 expression. These data indicate that overexpression of IL-4, which constitutes the primary inducer of Th2 polarization, may cause the Th2 bias of polyclonally stimulated KSRP -/- CD4 + T cells. This is the first report demonstrating that KSRP is involved in the regulation of T cell responses. We present strong evidence that T cells derived from KSRP -/- mice favor Th2-driven immune responses." @default.
• W2967507951 created "2019-08-22" @default.
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• W2967507951 date "2019-08-14" @default.
• W2967507951 modified "2023-10-15" @default.
• W2967507951 title "The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4⁺T Cells" @default.
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• W2967507951 doi "https://doi.org/10.1155/2019/4726532" @default.
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