β-カテニン安定化は、アンフィレグリンおよびBATFを介した制御性T細胞を介して肺胞出血を防御する

Alveolar hemorrhage (AH) is a life-threatening condition with high mortality, yet the immunologic mechanisms governing disease severity remain poorly defined. Here, we demonstrate a protective role for T cell-intrinsic β-catenin stabilization in AH using a transgenic mouse model (CAT-Tg) in which β-catenin is stabilized under the Lck promoter. β-Catenin stabilization induced a distinct T cell phenotype marked by expansion of central effector memory cells (CD44+CD122+Eomes+T-bet+) and suppression of proinflammatory signaling, including reduced phosphorylation of STAT1, STAT3, and JAK1. Pristane-induced AH was attenuated in CAT-Tg mice, which exhibited reduced lung injury, decreased proteinuria, and diminished pulmonary proinflammatory cytokine production compared with wild-type controls. Protection was associated with a marked expansion of FOXP3+ regulatory T cells (Tregs). Mechanistically, β-catenin stabilization enhanced lung expression of Amphiregulin and BATF, mediators of Treg stability and tissue repair. Adoptive transfer of CAT-Tg-derived Tregs into wild-type mice conferred superior protection against AH, reducing lung inflammation and proteinuria. Transcriptomic analyses revealed enrichment of tissue repair and immune homeostasis pathways, including PI3K-Akt, angiogenesis, and STAT5 signaling. Collectively, these findings identify β-catenin as a regulator of a protective Amphiregulin-BATF-Treg axis, highlighting a immunomodulatory pathway with therapeutic potential for AH and inflammatory lung disease.