Inflammation-induced pulmonary fibrosis (PF) leads to irreversible loss of lung function and is a predictor of mortality in numerous lung diseases. Why some subjects with lung inflammation but not others develop PF is unclear. In a mouse model of hypersensitivity pneumonitis that progresses to lung fibrosis upon repeated exposure to the ubiquitous microorganism Bacillus subtilis, γδ T cells expand in the lung and inhibit collagen deposition. We show that a subset of these γδ cells represents the predominant source of the Th17 cytokine IL-22 in this model. Preventing expression of IL-22, either by mutating the aryl hydrocarbon receptor (AhR) or inhibiting AhR signaling, accelerated lung fibrosis. Direct blockade of IL-22 also enhanced collagen deposition in the lung, whereas administration of recombinant IL-22 inhibited lung fibrosis. Moreover, the presence of protective γδ T cells and IL-22 diminished recruitment of CD4+ T cells to lung. These data reveal a protective pathway that involves the inhibition of αβ T cells by regulatory IL-22–secreting γδ T cells.
Deletion of mTORC1 Activity in CD4+ T Cells Is Associated with Lung Fibrosis and Increased γδ T Cells
