γδ T cells protect against lung fibrosis via IL-22.
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.
Simonian
Philip L
PL
Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Wehrmann
Fabian
F
Roark
Christina L
CL
Born
Willi K
WK
O'Brien
Rebecca L
RL
Fontenot
Andrew P
AP
D000818:Animals; D001412:Bacillus subtilis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000382:microbiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D000097043:Interleukin-22
D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22