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Tbx21 and foxp3 are Epigenetically Stabilized in T-Bet Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs.
Elfaki, Yassin ; Yang, Juhao ; Boehme, Julia ; Schultz, Kristin ; Bruder, Dunja ; Falk, Christine S ; Huehn, Jochen ; Floess, Stefan
Elfaki, Yassin
Yang, Juhao
Boehme, Julia
Schultz, Kristin
Bruder, Dunja
Falk, Christine S
Huehn, Jochen
Floess, Stefan
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2021-07-14
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Abstract
During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet- Tregs are epigenetically stabilized during IAV-induced infection in the lung.
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Int J Mol Sci. 2021 Jul 14;22(14):7522. doi: 10.3390/ijms22147522.
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en
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1422-0067
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Attribution 4.0 International
