In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 218, No. 12 ( 2021-12-06)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.20210639
Sprache:
Englisch
Verlag:
Rockefeller University Press
Publikationsdatum:
2021
ZDB Id:
1477240-1