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

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

  • J Exp Med. 2021 Dec 6;218(12):e20210639. doi: 10.1084/jem.20210639.
Takahiro Nakajima 1 Toshio Kanno 1 Satoru Yokoyama 1 Shigemi Sasamoto 1 Hikari K Asou 1 Damon J Tumes 2 Osamu Ohara 3 Toshinori Nakayama 4 5 Yusuke Endo 1 6
Affiliations

Affiliations

  • 1 Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan.
  • 2 Centre for Cancer Biology, University of South Australia, North Terrace, Adelaide, Australia.
  • 3 Department of Applied Genomics Kazusa DNA Research Institute, Chiba, Japan.
  • 4 Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • 5 AMED-CREST, AMED, Chiba, Japan.
  • 6 Department of Omics Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
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.

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