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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.
Afiliación
  • Elfaki Y; Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Yang J; Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Boehme J; Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Schultz K; Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Bruder D; Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Falk CS; Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
  • Huehn J; Institute of Transplant Immunology, Hannover Medical School, 30625 Hannover, Germany.
  • Floess S; German Center for Infection Research DZIF, Thematical Translation Unit-Immunocompromized Host (TTU-IICH), Hannover-Braunschweig Site, 30625 Hannover, Germany.
Int J Mol Sci ; 22(14)2021 Jul 14.
Article en En | MEDLINE | ID: mdl-34299148
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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Infecciones por Orthomyxoviridae / Linfocitos T CD8-positivos / Proteínas de Dominio T Box / Epigénesis Genética / Factores de Transcripción Forkhead / Pulmón Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Infecciones por Orthomyxoviridae / Linfocitos T CD8-positivos / Proteínas de Dominio T Box / Epigénesis Genética / Factores de Transcripción Forkhead / Pulmón Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania