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

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. The authors find that lung and skin pathogenic CD4(+) T cells express high levels of ACC1. ACC1 controls the inflammatory function of the pathogenic CD4(+) T cell population to promote type 2 inflammation in the lung and skin.

Automated summary

The study reveals that pathogenic CD4(+) T cells in the lungs and skin exhibit high levels of ACC1. ACC1 regulates the inflammatory function of pathogenic CD4(+) T cell population to promote type 2 inflammation in the lungs and skin.