In vivo reprogramming of pathogenic lung TNFR2+ cDC2s by IFNβ inhibits HDM-induced asthma

Asthma is a common inflammatory lung disease with no known cure. Previously, we uncovered a lung TNFR2+ conventional DC2 subset (cDC2s) that induces regulatory T cells (T-regs) maintaining lung tolerance at steady state but promotes T(H)2 response during house dust mite (HDM)-induced asthma. Lung IFN beta is essential for TNFR2+ cDC2s-mediated lung tolerance. Here, we showed that exogenous IFN. reprogrammed T(H)2-promoting pathogenic TNFR2+ cDC2s back to tolerogenic DCs, alleviating eosinophilic asthma and preventing asthma exacerbation. Mechanistically, inhaled IFN beta, not IFN beta, activated ERK2 signaling in pathogenic lung TNFR2+ cDC2s, leading to enhanced fatty acid oxidation (FAO) and lung Treg induction. Last, human IFN beta reprogrammed pathogenic human lung TNFR2+ cDC2s from patients with emphysema ex vivo. Thus, we identified an IFN beta-specific ERK2-FAO pathway that might be harnessed for DC therapy.

Automated summary

This study found that exogenous IFN beta can reprogram specific lung cells involved in asthma, alleviating symptoms and potentially being used for future treatments.