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

The paper investigates how pulmonary immune cells are spatially organized during fungal-induced type 2 inflammation, focusing on T helper 2 (TH2) cell positioning. Using a model of inflammation-expanded macrophages, the authors identify cholesterol-25-hydroxylase (CH25H)–expressing macrophages that produce 25-hydroxycholesterol, which is converted to the oxysterol 7α,25-dihydroxycholesterol that attracts GPR183-expressing TH2 cells into infectious lesions. They report that this TH2 localization suppresses interferon-γ responsiveness in inflammatory Ly6C+ macrophages, which promotes fungal persistence, and that TH2-specific GPR183 deletion disrupts the axis, restoring type 1 macrophage activation and enhancing fungal clearance. A limitation explicitly noted is that the work centers on a fungal pulmonary type 2 inflammation system and its metabolite-driven chemotactic mechanism rather than broader immune contexts. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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