Heterogeneity of regulatory T cells during lung inflammation

Abstract

Abstract Pulmonary inflammation is the leading cause of respiratory illness worldwide. Although strong T cell responses are desired for defending the hosts against infections, the cytotoxic effector function of the innate and adaptive immune responses can lead to the development of pulmonary immunopathology, which may lead to death. While T cells produce inflammatory cytokines during infections and allergies, they can also produce the immunomodulatory cytokine IL-10, which is critical for limiting the immunopathology caused by the excessive effector immune responses. However, the composition of IL-10-producing lymphocyte population and their molecular signatures are unclear. Using mouse models that report the production of IL-10 by GFP and expression of T regulatory cell marker Foxp3 by RFP, mouse models of lung inflammation (including allergic asthma, hypersensitivity pneumonitis, and flu), transcriptomic analyses at the population and single cell levels, and transgenic mouse models that are impaired in T cell-derived IL-10 production, we found that, in the disease models used, regulatory T cells in the mouse airway are mainly comprised of CD4+ Foxp3+, CD4+ Foxp3− and CD8+ subsets, and they differ under different disease conditions. Furthermore, within each subset, IL-10-producing T cells exhibit significant molecular heterogeneity. Information gained from this dataset provides insights into the T cell subset heterogeneity and signature markers, and shed light for future strategic design for therapeutic development utilizing the immunomodulatory features of T cells for the treatment of pulmonary immunopathology.