Spatial organization of pulmonary type 2 inflammation by a macrophage-derived cholesterol metabolite.

ABSTRACT: Effective pulmonary immunity requires the precise spatial organization of immune cells, yet the mechanisms guiding their intratissue positioning during inflammation remain unclear. Here, we identify a cholesterol-derived chemotactic axis that spatially organizes T helper 2 (T_H2) cells during fungal-induced pulmonary type 2 inflammation. Inflammation-expanded macrophages expressing cholesterol-25-hydroxylase (CH25H) produce 25-hydroxycholesterol, which is converted into the oxysterol 7α,25-dihydroxycholesterol to attract GPR183-expressing T_H2 cells into infectious lesions. This T_H2 positioning suppresses interferon-γ responsiveness in inflammatory Ly6C⁺ macrophages, promoting fungal persistence. Disruption of this axis via T_H2-specific GPR183 dele

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC12324256 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature