Sjögren's syndrome: studying the disease in mice

Delaleu, Nicolas; Nguyen, Cuong Q.; Peck, Ammon B.; Jönsson, Roland

doi:10.1186/ar3313

Cited by 88 publications

(86 citation statements)

References 135 publications

(197 reference statements)

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“…The late disease onset and the diverse genetic background of affected individuals complicate study of the disease mechanism and pathogenesis. Although several mouse models display a pSS-like phenotype (17)(18)(19)(20)(21), no single model can perfectly match the full spectrum of pSS observed in humans.…”

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confidence: 99%

STIM1 and STIM2 protein deficiency in T lymphocytes underlies development of the exocrine gland autoimmune disease, Sjögren's syndrome

Cheng¹,

Alevizos

Liu³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Primary Sjögren's Syndrome (pSS) is an autoimmune disease involving salivary and other exocrine glands that leads to progressive lymphocytic infiltration into the gland, tissue damage, and secretory defects. The mechanism underlying this disease remains poorly understood. Here we report that mice with T-cell–targeted deletion of Stromal Interaction Molecule (STIM) 1 and STIM2 [double-knockout (DKO)] mice develop spontaneous and severe pSS-like autoimmune disease, displaying major hallmarks of the disease. In DKO mice, diffuse lymphocytic infiltration was seen in submandibular glands, a major target of pSS, by age 6 wk, progressing to severe inflammation by age 12 wk. Sjögren's syndrome-specific autoantibodies (SSA/Ro and SSB/La) were detected in the serum, and progressive salivary gland destruction and loss of fluid secretion were also seen. Importantly, we report that peripheral blood mononuclear cells as well as lymphocytic infiltrates in submandibular glands from patients with pSS demonstrated significant reductions in STIM1 and STIM2 proteins. Store-operated calcium entry was also reduced in peripheral blood mononuclear cells from pSS patients compared with those from healthy controls. Thus, deficiency of STIM1 and STIM2 proteins in T cells, and consequent defects in Ca 2+ signaling, are associated with salivary gland autoimmunopathy in DKO mice and pSS patients. These data reveal a previously unreported link between STIM1 and STIM2 proteins and pSS.

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confidence: 99%

STIM1 and STIM2 protein deficiency in T lymphocytes underlies development of the exocrine gland autoimmune disease, Sjögren's syndrome

Cheng¹,

Alevizos

Liu³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…type I Interferon receptor Deficiency prevents Murine sjögren's syndrome Currently, there are several mouse models for SS described in the literature, and each model has its advantages and disadvantages for investigating this complicated disorder (Delaleu et al, 2011). Since the IFNAR deficiency was on the C57BL/6 (B6) background (Yasuda et al, 2007), we used the B6.Aec1Aec2 mouse for our study.…”

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confidence: 99%

Type I Interferon Receptor Deficiency Prevents Murine Sjögren’s Syndrome

et al. 2013

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In Sjögren's Syndrome (SS), inherent glandular defects, autoimmunity, and mononuclear cell infiltration within the salivary glands cause reduced salivation leading to xerostomia. Excessive production of type I interferons (IFN), triggered by environmental and genetic factors, is considered pathogenic in this disorder. However, whether type I IFN production is causative or an outcome of the disease process is not known. To address this question, we introduced a deficiency of interferon alpha receptor 1 (Ifnar1) into B6.Aec1Aec2 mice, which are known to have the genetic loci necessary for developing a SS-like disorder. This new mouse strain, B6.Aec1Aec2Ifnar1 -/-, lacking type I IFN-mediated signaling, was characterized for pilocarpine-induced salivation, the presence of serum autoantibodies, sialoadenitis, and dacryoadenitis. Compared with the B6.Aec1Aec2Ifnar1 +/+ (wild-type) mice, the B6.Aec1Aec2Ifnar1 -/-(knockout) mice had significantly lower mononuclear cell infiltration in the salivary and lacrimal glands. The knockout mice were completely protected from salivary gland dysfunction. Surprisingly, they had a robust autoantibody response comparable with that of the wild-type mice. These findings demonstrate that, in the absence of type I IFN-mediated signaling, systemic autoantibody responses can be dissociated from glandular pathology. Our study suggests that, in genetically susceptible individuals, the type I IFN pathway can instigate certain features of SS.

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“…Interestingly, Hashimoto's thyroiditis can be present in about 30% of SS patients (Chiorini et al, 2009), so it is perhaps not surprising that NOD.H-2h4 mice also spontaneously develop SS. NOD mice, which are closely related to NOD.H-2h4 mice, also develop SS (Chiorini et al, 2009;Delaleu, Nguyen, Peck, & Jansson, 2011). In this section, we review what is known about SS in WT NOD.H-2h4 mice and describe mutant strains of NOD.H-2h4 mice that have a higher incidence of SS.…”

Section: Ss In Nodh-2h4 Mice and Nodh-2h4 Mutantsmentioning

confidence: 98%