ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice
Open Access
- 23 November 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (12)
- https://doi.org/10.1084/jem.20210639
Abstract
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.Funding Information
- Ministry of Education, Culture, Sports, Science and Technology (18H04665, 20H03455, 20K21618, 26221305, JP19H05650)
- The Nakajima Foundation
- Terumo Foundation for Life Sciences and Arts
- Tokyo Biochemical Research Foundation
- Kato Memorial Bioscience Foundation
- Hamaguchi Foundation for the Advancement of Biochemistry
- Suzuken Memorial Foundation
- Kanae Foundation for the Promotion of Medical Science
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- GlaxoSmithKline Japan (2019)
- SENSHIN Medical Research Foundation
- Sumitomo Foundation
- Koyanagi Foundation
- Kishimoto Foundation 2019
- Uehara Memorial Foundation
- Nakatomi Foundation
- Research Foundation for Pharmaceutical Sciences Group A
- Cell Science Research Foundation
- Astellas Foundation for Research on Metabolic Disorders
- MSD Life Science Foundation, Public Interest Incorporated Foundation
- Nagase Science Technology Foundation
- Japan Agency for Medical Research and Development (JP21ek0410060)
- AMED-CREST (JP21gm1210003)
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