gd T cells protect against lung fibrosis via IL-22

• Published in: The Journal of experimental medicine Vol. 207; no. 10; pp. 2239 - 2253
• Main Authors: Simonian, Philip L, Wehrmann, Fabian, Roark, Christina L, Born, Willi K, O'Brien, Rebecca L, Fontenot, Andrew P
• Format: Journal Article
• Language: English
• Published: 01.01.2010
• Subjects: Bacillus subtilis
• ISSN: 0022-1007

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, gd T cells expand in the lung and inhibit collagen deposition. We show that a subset of these gd 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 gd T cells and IL-22 diminished recruitment of CD4+ T cells to lung. These data reveal a protective pathway that involves the inhibition of ab T cells by regulatory IL-22-secreting gd T cells.