CD103^hi T_reg cells constrain lung fibrosis induced by CD103^lo tissue-resident pathogenic CD4 T cells

Tissue-resident memory T cells (T_RM cells) are crucial mediators of adaptive immunity in nonlymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4⁺ T_RM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69^hiCD103^lo CD4⁺ T_RM cells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69^hiCD103^hiFoxp3⁺ CD4⁺ regulatory T cells were induced and constrained the ability of pathogenic CD103^lo T_RM cells to cause fibrosis. Thus, lung tissue-resident CD4⁺ T cells play crucial roles in the pathology of chronic lung inflammation, and CD103 expression defines pathogenic effector and immunosuppressive tissue-resident cell subpopulations in the inflamed lung.