Tomomi Ichikawa, Kiyoshi Hirahara, Kota Kokubo, Masahiro Kiuchi, Ami Aoki, Yuki Morimoto, Jin Kumagai, Atsushi Onodera, Naoko Mato, Damon J Tumes, Yoshiyuki Goto, Koichi Hagiwara, Yutaka Inagaki, Tim Sparwasser, Kazuyuki Tobe, Toshinori Nakayama
Nature immunology 20(11) 1469-1480 2019年11月 査読有り
Tissue-resident memory T cells (TRM cells) are crucial mediators of adaptive immunity in nonlymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4+ TRM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69hiCD103lo CD4+ TRM cells 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 CD103lo TRM 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.