| First Author | Simonian PL | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 10 | Pages | 2239-53 |
| PubMed ID | 20855496 | Mgi Jnum | J:165803 |
| Mgi Id | MGI:4838483 | Doi | 10.1084/jem.20100061 |
| Citation | Simonian PL, et al. (2010) gammadelta T cells protect against lung fibrosis via IL-22. J Exp Med 207(10):2239-53 |
| abstractText | 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, gammadelta T cells expand in the lung and inhibit collagen deposition. We show that a subset of these gammadelta 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 gammadelta T cells and IL-22 diminished recruitment of CD4(+) T cells to lung. These data reveal a protective pathway that involves the inhibition of alphabeta T cells by regulatory IL-22-secreting gammadelta T cells. |
