Lung IFNAR1^hi TNFR2⁺ cDC2 promotes lung regulatory T cells induction and maintains lung mucosal tolerance at steady state.

ABSTRACT: The lung is a naturally tolerogenic organ. Lung regulatory T cells (T-regs) control lung mucosal tolerance. Here, we identified a lung IFNAR1^hiTNFR2⁺ conventional DC2 (iR2D2) population that induces T-regs in the lung at steady state. Using conditional knockout mice, adoptive cell transfer, receptor blocking antibodies, and TNFR2 agonist, we showed that iR2D2 is a lung microenvironment-adapted dendritic cell population whose residence depends on the constitutive TNFR2 signaling. IFNβ-IFNAR1 signaling in iR2D2 is necessary and sufficient for T-regs induction in the lung. The Epcam⁺CD45^- epithelial cells are the sole lung IFNβ producer at the steady state. Surprisingly, iR2D2 is plastic. In a house dust mite model of asthma, iR2D2 generates lung T<

SUBMITTER: Mansouri S 

PROVIDER: S-EPMC7311323 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature