title: Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance.
abstract: Interstitial lung disease (ILD) is a common manifestation of systemic autoimmunity characterized by progressive inflammation or scarring of the lungs. Patients who develop these complications can exhibit significantly impaired gas exchange that may result in hypoxemia, pulmonary hypertension, and even death. Unfortunately, little is understood about how these diseases arise, including the role of specific defects in immune tolerance. Another key question is whether autoimmune responses targeting the lung parenchyma are critical to ILD pathogenesis, including that of isolated idiopathic forms. We show that a specific defect in central tolerance brought about by mutations in the autoimmune regulator gene (Aire) leads to an autoreactive T cell response to a lung antigen named vomeromodulin and the development of ILD. We found that a human patient and mice with defects in Aire develop similar lung pathology, demonstrating that the AIRE-deficient model of autoimmunity is a suitable translational system in which to unravel fundamental mechanisms of ILD pathogenesis.
authors.affiliation: 1Diabetes Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Shum
authors.forename: Jason
authors.initials: J
authors.lastname: DeVoss
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Tan
authors.forename: Yafei
authors.initials: Y
authors.lastname: Hou
authors.forename: Kellsey
authors.initials: K
authors.lastname: Johannes
authors.forename: Clodagh S
authors.initials: CS
authors.lastname: O'Gorman
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Jones
authors.forename: Etienne B
authors.initials: EB
authors.lastname: Sochett
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fong
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001324:Autoantigens / Q000032:analysis*; D017563:Lung Diseases, Interstitial / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000096927:AIRE Protein
chemical_list: D001324:Autoantigens; D014157:Transcription Factors; D000096927:AIRE Protein