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- W4313359493 abstract "Abstract Recently, a critical role of CTLA-4 in a regulatory T cell (Treg) function has been highlighted both in peripheral and follicular regulatory T cells. However, the importance of cytoplasmic domain CTLA-4 signaling in Treg function and differentiation is not clearly understood. In this study, we utilized a recombinant extracellular domain (CTLA-4-Ig) and cytoplasmic domain of CTLA-4 (dNP2-ctCTLA-4) to elucidate the mechanism of CTLA-4 in Tregs. We found dNP2-ctCTLA-4 increased follicular regulatory T (Tfr) cells in draining lymph node (dLN), accompanying by decreased level of follicular helper T (Tfh) cells and germinal center (GC) B cells, while CTLA-4-Ig only reduced Tfh cells and GC B cells without affects on Tfr cells. In addition, dNP2-ctCTLA-4 induces Foxp3 positive regulatory T cells in Th17 and Th1 conditions with TGF-β, while CTLA-4-Ig inhibited effector cytokine productions without affecting Foxp3 levels. One of the molecular mechanism of dNP2-ctCTLA-4 in Foxp3 expression would be inhibition of Jak2/STAT3 pathway via binding to Jak2 which inhibits Th17. In addition, TGF-β signaling was enhanced by it via inhibition of phosphorylation on Erk and Smad2 linker region to results increasing Foxp3 expression in T cells. These results suggest that the cytoplasmic domain CTLA-4 signaling would be critical to support immune homeostatic environments in dLN via enhancing Foxp3 expression in T cells." @default.
- W4313359493 created "2023-01-06" @default.
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- W4313359493 date "2018-05-01" @default.
- W4313359493 modified "2023-10-16" @default.
- W4313359493 title "The cytoplasmic domain of CTLA-4 inhibits effector T cell responses and autoimmunity via increasing regulatory T cells in mice" @default.
- W4313359493 doi "https://doi.org/10.4049/jimmunol.200.supp.110.17" @default.
- W4313359493 hasPublicationYear "2018" @default.
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