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

J Leukoc Biol. 2017 Dec;102(6):1411-1420. doi: 10.1189/jlb.3A0717-311R. Epub 2017 Sep 26.


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.

Keywords: NOD.B10; autoantibody; extraglandular disease; saliva.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • Autoantibodies / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Cross-Linking Reagents / metabolism
  • Disease Models, Animal
  • Disease Progression*
  • Inflammation / pathology
  • Kidney / drug effects
  • Kidney / pathology
  • Lacrimal Apparatus / drug effects
  • Lacrimal Apparatus / pathology
  • Lipopolysaccharides / pharmacology
  • Lung / drug effects
  • Lung / pathology
  • Mice, Inbred NOD
  • Myeloid Differentiation Factor 88 / metabolism*
  • Receptors, Antigen, B-Cell / metabolism
  • Salivary Glands / drug effects
  • Salivary Glands / pathology
  • Salivary Glands / physiopathology
  • Salivation / drug effects
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / metabolism*
  • Sjogren's Syndrome / pathology*
  • Sjogren's Syndrome / physiopathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Antibodies, Antinuclear
  • Autoantibodies
  • Cross-Linking Reagents
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • Receptors, Antigen, B-Cell