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Myd88 is required for disease development in a primary Sjögren's syndrome mouse model.

Authors
  • Kiripolsky, Jeremy1
  • McCabe, Liam G1
  • Gaile, Daniel P2
  • Kramer, Jill M3, 4
  • 1 Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA.
  • 2 Department of Biostatistics, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, New York, USA; and.
  • 3 Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA; [email protected]
  • 4 Department of Oral Diagnostic Sciences, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Type
Published Article
Journal
Journal of Leukocyte Biology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2017
Volume
102
Issue
6
Pages
1411–1420
Identifiers
DOI: 10.1189/jlb.3A0717-311R
PMID: 28951424
Source
Medline
Keywords
Language
English
License
Unknown

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-H2b /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. © Society for Leukocyte Biology.

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