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- W4313365875 abstract "Abstract CD4+ T helper 1 (TH1) cells are essential mediators of immune responses directed against viruses and intracellular bacteria. As such, elucidation of the regulatory mechanisms underlying their development and function is necessary to direct the function of these cells in immunotherapeutic approaches to treat human disease. Recently, we demonstrated that the Ikaros zinc finger (IkZF) factor Aiolos cooperates with STAT3 to induce Bcl-6 expression in CD4+ T follicular helper (TFH) cells. Given conservation between individual members of the IkZF and STAT families, we hypothesized that additional IkZF/STAT complexes may regulate the development of other T cell subsets. Indeed, we find that the expression of the IkZF factor Eos is elevated in TH1 cells compared to TFH and naive CD4+ T cell subsets. We further find that induction of Eos expression is dependent on IL-2 signaling and is mediated, in part, by STAT5. Furthermore, expression of TH1 markers, including Blimp-1, IL-2rα, and IL-2rβ, as well as the production of the TH1-associated cytokine, IFN-γ were significantly diminished in Eos-deficient TH1 cells. Mechanistically, we found that Eos physically interacts with STAT5 and that these factors are co-enriched at the Prdm1 and Il2ra gene loci in TH1 cells. Intriguingly, we also found that Eos-deficient CD8+ cells differentiated under TC1-polarizing conditions displayed reduced expression of the TC1 genes encoding T-bet, Blimp-1, IFN-γ, and Granzyme B. Collectively, our data support a conserved role for a regulatory axis involving IL-2, STAT5, and Eos that drives the differentiation and function of CD4+ TH1 and CD8+ TC1 cells." @default.
- W4313365875 created "2023-01-06" @default.
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- W4313365875 date "2019-05-01" @default.
- W4313365875 modified "2023-09-23" @default.
- W4313365875 title "The Ikaros zinc finger transcription factor Eos regulates CD4+ TH1 and CD8+ TC1 differentiation programs" @default.
- W4313365875 doi "https://doi.org/10.4049/jimmunol.202.supp.128.8" @default.
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