Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 207, Issue 10, Pages 2239-2253Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100061
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Funding
- National Institutes of Health [HL062410, ES011810, HL089766]
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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, gamma delta T cells expand in the lung and inhibit collagen deposition. We show that a subset of these gamma delta 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 gamma delta T cells and IL-22 diminished recruitment of CD4(+) T cells to lung. These data reveal a protective pathway that involves the inhibition of alpha beta T cells by regulatory IL-22-secreting gamma delta T cells.
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