Myd88 is required for disease development in a primary Sjögren's syndrome mouse model. Issue 6 (26th September 2017)

• Record Type: Journal Article
• Authors: Kiripolsky, Jeremy; McCabe, Liam G; Gaile, Daniel P; Kramer, Jill M
• Is Part Of: Journal of leukocyte biology. Volume 102:Issue 6(2017)
• Page Start: 1411
• Page End: 1420
• Publication Date: 2017-09-26
• Subjects: saliva -- autoantibody -- NOD.B10 -- extraglandular disease; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0717-311R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Murine model of primary Sjögren's syndrome establishes Myd88 as a crucial mediator of local and systemic disease manifestations. Abstract: Sjögren's syndrome (SS) is an autoimmune disease that often results in diminished exocrine gland function. SS patients also experience systemic disease manifestations, including hypergammaglobulinemia and pulmonary and renal pathoses. MyD88 is a ubiquitously expressed adaptor molecule used by all immune cells that is required for IL-1 receptor (IL-1R), IL-18R, and most TLR signaling. The precise role of MyD88 in SS has not been evaluated, although this adaptor is critical for development of lupus, a related autoimmune disease. This study tested the hypothesis that Myd88-mediated signaling is required for local and systemic SS manifestations. To this end, we generated NOD.B10Sn- H2 b /J (NOD.B10) mice that are deficient in Myd88 (NOD.B10 Myd88−/− ). We found that NOD.B10 animals that lack Myd88 show reduced exocrine and extraglandular inflammation. Moreover, these animals are protected from loss of salivary flow. Splenocytes from NOD.B10 Myd88−/− mice did not up-regulate activation markers or secrete IL-6 in response to a Myd88-dependent agonist, although BCR signaling remained intact. Finally, IgM, IgG, and anti-nuclear autoantibodies were reduced in NOD.B10 Myd88−/− mice compared with the parental strain. These data demonstrate that Myd88 is a crucial mediator of local and systemic SS disease manifestations.