| First Author | Mansouri S | Year | 2020 |
| Journal | Mucosal Immunol | Volume | 13 |
| Issue | 4 | Pages | 595-608 |
| PubMed ID | 31959883 | Mgi Jnum | J:294794 |
| Mgi Id | MGI:6445366 | Doi | 10.1038/s41385-020-0254-1 |
| Citation | Mansouri S, et al. (2020) Lung IFNAR1(hi) TNFR2(+) cDC2 promotes lung regulatory T cells induction and maintains lung mucosal tolerance at steady state. Mucosal Immunol 13(4):595-608 |
| abstractText | The lung is a naturally tolerogenic organ. Lung regulatory T cells (T-regs) control lung mucosal tolerance. Here, we identified a lung IFNAR1(hi)TNFR2(+) 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. IFNbeta-IFNAR1 signaling in iR2D2 is necessary and sufficient for T-regs induction in the lung. The Epcam(+)CD45(-) epithelial cells are the sole lung IFNbeta producer at the steady state. Surprisingly, iR2D2 is plastic. In a house dust mite model of asthma, iR2D2 generates lung TH2 responses. Last, healthy human lungs have a phenotypically similar tolerogenic iR2D2 population, which became pathogenic in lung disease patients. Our findings elucidate lung epithelial cells IFNbeta-iR2D2-T-regs axis in controlling lung mucosal tolerance and provide new strategies for therapeutic interventions. |
