title: Type I interferon receptor deficiency prevents murine Sjogren's syndrome.
abstract: In Sjögren's Syndrome (SS), inherent glandular defects, autoimmunity, and mononuclear cell infiltration within the salivary glands cause reduced salivation leading to xerostomia. Excessive production of type I interferons (IFN), triggered by environmental and genetic factors, is considered pathogenic in this disorder. However, whether type I IFN production is causative or an outcome of the disease process is not known. To address this question, we introduced a deficiency of interferon alpha receptor 1 (Ifnar1) into B6.Aec1Aec2 mice, which are known to have the genetic loci necessary for developing a SS-like disorder. This new mouse strain, B6.Aec1Aec2Ifnar1 (-/-), lacking type I IFN-mediated signaling, was characterized for pilocarpine-induced salivation, the presence of serum autoantibodies, sialoadenitis, and dacryoadenitis. Compared with the B6.Aec1Aec2Ifnar1 (+/+) (wild-type) mice, the B6.Aec1Aec2Ifnar1 (-/-) (knockout) mice had significantly lower mononuclear cell infiltration in the salivary and lacrimal glands. The knockout mice were completely protected from salivary gland dysfunction. Surprisingly, they had a robust autoantibody response comparable with that of the wild-type mice. These findings demonstrate that, in the absence of type I IFN-mediated signaling, systemic autoantibody responses can be dissociated from glandular pathology. Our study suggests that, in genetically susceptible individuals, the type I IFN pathway can instigate certain features of SS.
authors.affiliation: Division of Nephrology, Center for Immunity Inflammation and Regenerative Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Szczerba
authors.forename: P D
authors.initials: PD
authors.lastname: Rybakowska
authors.forename: P
authors.initials: P
authors.lastname: Dey
authors.forename: K M
authors.initials: KM
authors.lastname: Payerhin
authors.forename: A B
authors.initials: AB
authors.lastname: Peck
authors.forename: H
authors.initials: H
authors.lastname: Bagavant
authors.forename: U S
authors.initials: US
authors.lastname: Deshmukh
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D003607:Dacryocystitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012472:Salivation / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012793:Sialadenitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D001323:Autoantibodies; D053633:Receptor, Interferon alpha-beta