CD103hiTregcells constrain lung fibrosis induced by CD103lotissue-resident pathogenic CD4 T cells

Tissue-resident memory T cells (TRMcells) are crucial mediators of adaptive immunity in nonlymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4+TRMcells that reside within chronic inflammatory lesions remain unknown. We found that CD69hiCD103loCD4+TRMcells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69hiCD103hiFoxp3+CD4+regulatory T cells were induced and constrained the ability of pathogenic CD103loTRMcells 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.