calcipotriene and Pneumonia

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.

Topics: Acetyl-CoA Carboxylase; Administration, Topical; Animals; Basophils; Calcitriol; CD4-Positive T-Lymphocytes; Drug Eruptions; Fatty Acids; Granulocyte-Macrophage Colony-Stimulating Factor; Interleukin-3; Interleukin-5; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Pneumonia; Th2 Cells