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ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice

T cells possess distinguishing effector functions and drive inflammatory disorders. We have previously identified IL-5–producing Th2 cells as the pathogenic population predominantly involved in the pathology of allergic inflammation. However, the cell-intrinsic signaling pathways that control the pa...

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Detalles Bibliográficos
Autores principales: Nakajima, Takahiro, Kanno, Toshio, Yokoyama, Satoru, Sasamoto, Shigemi, Asou, Hikari K., Tumes, Damon J., Ohara, Osamu, Nakayama, Toshinori, Endo, Yusuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614157/
https://www.ncbi.nlm.nih.gov/pubmed/34813654
http://dx.doi.org/10.1084/jem.20210639
Descripción
Sumario:T cells possess distinguishing effector functions and drive inflammatory disorders. We have previously identified IL-5–producing Th2 cells as the pathogenic population predominantly involved in the pathology of allergic inflammation. However, the cell-intrinsic signaling pathways that control the pathogenic Th2 cell function are still unclear. We herein report the high expression of acetyl-CoA carboxylase 1 (ACC1) in the pathogenic CD4(+) T cell population in the lung and skin. The genetic deletion of CD4(+) T cell–intrinsic ACC1 dampened eosinophilic and basophilic inflammation in the lung and skin by constraining IL-5 or IL-3 production. Mechanistically, ACC1-dependent fatty acid biosynthesis induces the pathogenic cytokine production of CD4(+) T cells via metabolic reprogramming and the availability of acetyl-CoA for epigenetic regulation. We thus identified a distinct phenotype of the pathogenic T cell population in the lung and skin, and ACC1 was shown to be an essential regulator controlling the pathogenic function of these populations to promote type 2 inflammation.