The osteopontin transgenic mouse is a new model for Sjögren's syndrome

Abstract

Osteopontin (Opn) is a cytokine involved in both physiological and pathological processes, and is elevated in many autoimmune diseases. Sjögren’s syndrome (SS) is an autoimmune disease with a strong female predilection characterized by lymphocytic infiltration of exocrine glands. We hypothesized Opn contributes to SS pathogenesis. We examined an established SS model, and found increased Opn locally and systemically. Next, we examined Opn transgenic (Opn Tg) mice for evidence of SS. Opn Tg animals exhibited lymphocytic infiltration of salivary and lacrimal glands, and Opn co-localized with the infiltrates. Moreover, saliva production was reduced, and SS autoantibodies were observed in the serum of these mice. Finally, female Opn Tg mice showed more severe disease compared to males. Taken together, these data support a role for Opn in SS pathogenesis. We identify a new model of spontaneous SS that recapitulates the human disease in terms of sex predilection, histopathology, salivary deficits, and autoantibodies.

BAFF overexpression increases lymphocytic infiltration in Sjögren's target tissue, but only inefficiently promotes ectopic B-cell differentiation

“…Because not all mouse models of pSS rely on the same pathogenic mechanisms, the effect of BAFF could vary depending on the pathogenic context. Future studies are thus warranted to explore the impact of BAFF overexpression in other animal models of pSS such as the IL14 Tg mouse line which recapitulates many features of human pSS and spontaneously develops lymphoma [42] or the osteopontin transgenic mouse line, which also shares many features with the human disease including sex predilection, histopathology, salivary deficits, and autoantibodies [43].…”

Identification of Novel CD4+ T Cell Subsets in the Target Tissue of Sjögren’s Syndrome and Their Differential Regulation by the Lymphotoxin/LIGHT Signaling Axis

“…In these strains, CD4 + T cells with a PD1 high CD44 high CD62L low phenotype were shown to secrete large amounts of osteopontin in spleen and kidney and were characterized as pathogenic. The pathogenic role of osteopontin remains to be explored in pSS, but it is noteworthy that Spp1-transgenic mice develop a pSS-like phenotype (44). Importantly, the pathogenicity of this subset in lupus-prone strains is Slamf6 dependent, and Slamf6 was strongly upregulated in LGT-resident Th1 cells in NOD mice.…”

Contribution of HIV Infection, AIDS, and Antiretroviral Therapy to Exocrine Pathogenesis in Salivary and Lacrimal Glands

“…Furthermore, compared to DILS, in SS, HLA haplotypes tend to be distinctive and the CD4 + /CD8 + ratio is usually normal [ 116 ]. Recently, the role of osteopontin in contributing to SS pathogenesis has been investigated [ 129 ]. On the other hand, plasma osteopontin levels were previously suggested to be elevated in HIV patients despite ART [ 130 ].…”