ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice.
Takahiro NakajimaToshio KannoSatoru YokoyamaShigemi SasamotoHikari K AsouDamon J TumesOsamu OharaToshinori NakayamaYusuke EndoPublished in: The Journal of experimental medicine (2021)
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.
Keyphrases
- oxidative stress
- fatty acid
- soft tissue
- wound healing
- induced apoptosis
- single cell
- signaling pathway
- regulatory t cells
- dendritic cells
- transcription factor
- metabolic syndrome
- cell proliferation
- cell cycle arrest
- cell death
- long non coding rna
- genetic diversity
- genome wide
- copy number
- binding protein
- insulin resistance
- pi k akt