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.
ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 18H04665,20H03455,20K21618,26221305,JP19H05650
- Award Id(s): 2019
- Award Id(s): JP21ek0410060
- Award Id(s): JP21gm1210003
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Takahiro Nakajima, Toshio Kanno, Satoru Yokoyama, Shigemi Sasamoto, Hikari K. Asou, Damon J. Tumes, Osamu Ohara, Toshinori Nakayama, Yusuke Endo; ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice. J Exp Med 6 December 2021; 218 (12): e20210639. doi: https://doi.org/10.1084/jem.20210639
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