| First Author | Kiripolsky J | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 102 |
| Issue | 6 | Pages | 1411-1420 |
| PubMed ID | 28951424 | Mgi Jnum | J:250771 |
| Mgi Id | MGI:6103044 | Doi | 10.1189/jlb.3A0717-311R |
| Citation | Kiripolsky J, et al. (2017) Myd88 is required for disease development in a primary Sjogren's syndrome mouse model. J Leukoc Biol 102(6):1411-1420 |
| abstractText | Sjogren''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. |
