Open AccessACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice
Author(s) -
Takahiro Nakajima,
Toshio Kanno,
Satoru Yokoyama,
Shigemi Sasamoto,
Hikari K. Asou,
Damon J. Tumes,
Osamu Ohara,
Toshinori Nakayama,
Yusuke Endo
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20210639
Subject(s) - inflammation , biology , population , immunology , t cell , effector , phenotype , microbiology and biotechnology , immune system , genetics , medicine , gene , environmental health
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.