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- W2885251954 abstract "ABSTRACT The Tec kinases ITK (interleukin-2-inducible T-cell kinase) and RLK (resting lymphocyte kinase) are critical components of the proximal TCR/CD3 signal transduction machinery, and data in mice suggest that ITK negatively regulates T REG differentiation. However, whether Tec kinases modulate T REG development and/or function in human T cells remains unknown. Using a novel self-delivery siRNA platform (sdRNA), we found that ITK knockdown in primary human naïve peripheral blood CD4 T cells increased Foxp3 + T REG differentiation under both T REG and T effector (Teff) cell priming conditions. ITK knockdown also enhanced the expression of the co-inhibitory receptor PD-1 on FoxP3+ T cells. T REGS differentiated in vitro (iT REG ) after ITK knockdown displayed suppressive capacity against effector CD4+ T cell proliferation. ITK knockdown decreased IL-17A production in T cells primed under Th17 conditions and increased Th1 differentiation. Finally, a dual ITK/RLK Tec kinase inhibitor blocked T REG differentiation and T cell activation in general. Our data suggest that targeting ITK in human T cells may be an effective approach to boost T REG in the context of autoimmune diseases, but non-specific inhibition of other Tec family kinases may broadly inhibit T cell activation." @default.
- W2885251954 created "2018-08-22" @default.
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- W2885251954 date "2018-08-07" @default.
- W2885251954 modified "2023-09-24" @default.
- W2885251954 title "A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ TREG differentiation" @default.
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- W2885251954 doi "https://doi.org/10.1101/386508" @default.
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