title: IL-17A Blockade Attenuates Obliterative Bronchiolitis and IFN-γ Cellular Immune Response in Lung Allografts.
abstract: Obliterative bronchiolitis (OB), characterized by fibrous obliteration of the small airways, is a major impediment to long-term survival in lung allograft recipients. We found previously that IL-17A is produced primarily by CD4+T cells and γδ T cells after lung transplant in a mouse model of orthotopic lung transplant. The absence of either subset of T cells was compensated for by expansion of the other subset, which suggested that systemic blockade of IL-17A was necessary. To determine the specific role of IL-17A in the development of OB, we treated lung allograft recipients with an IL-17A antagonistic antibody. After IL-17A blockade, the incidence of OB was significantly reduced in lung allografts. IL-17A blockade also significantly attenuated the severity of acute rejection and overall lung fibrosis. The decreased OB incidence was associated with reduced lymphocyte recruitment, particularly CD8+T cells and other IFN-γ-producing lymphocytes, to the lung allograft. Interestingly, IL-17A blockade led to an increase in the frequency of IL-17A-producing T-helper cell type 17 cells and γδ T cells in lung allografts, suggesting that IL-17A is a negative regulator of these T cells. Our data suggest that blocking IL-17A after lung transplant reduces the overall IFN-γ-mediated lymphocyte response and decreases the development of OB.
authors.affiliation: 1 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and.
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Gupta
authors.affiliation: 1 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Wagner
authors.affiliation: 1 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: 1 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and.|2 Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Rebecca A
authors.identifier: 0000-0002-6326-2150
authors.initials: RA
authors.lastname: Shilling
mesh_terms: D064591:Allografts / Q000276:immunology*; D000818:Animals; D001989:Bronchiolitis Obliterans / Q000150:complications / Q000276:immunology* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D007111:Immunity, Cellular / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D016040:Lung Transplantation; D008297:Male; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000150:complications / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D007371:Interferon-gamma
keywords: IL-17; lung transplant; obliterative bronchiolitis