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

Nat Immunol. 2019 Nov;20(11):1469-1480. doi: 10.1038/s41590-019-0494-y. Epub 2019 Oct 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Fungal / immunology
  • Aspergillus fumigatus / immunology
  • Cell Communication / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Immune Tolerance*
  • Immunologic Memory*
  • Integrin alpha Chains / metabolism
  • Lung / cytology
  • Lung / immunology
  • Lung / pathology
  • Male
  • Mice, Transgenic
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Antigens, CD
  • Antigens, Fungal
  • Cytokines
  • Integrin alpha Chains
  • alpha E integrins