IDD3 and IDD5 Alleles From Nod Mice Mediate Sjögren’s Syndrome-Like Autoimmunity

Cha, Seunghee; Nagashima, Hiroyuki; Peck, Ammon B.; Humphreys‐Beher, Michael G.

doi:10.1007/978-1-4615-0717-8_146

Cited by 10 publications

(13 citation statements)

References 6 publications

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“…Similarly, pSS patients also have elevated IL-7 levels in the target organs and circulation [27]. Our recent study [28] showed that administration of exogenous IL-7 accelerates, whereas blockade of endogenous IL-7 inhibits the development and onset of pSS in C57BL/6.NOD- Aec1Aec2 (B6.NOD- Aec ) mice, a well-defined model of pSS [29,30]. Moreover, similar to the other autoimmune disorders, the promoting effects of IL-7 on pSS are underpinned by enhanced Th1 and Tc1 responses in the target organs [28].…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Signaling Induces Interleukin-7 Production from Salivary Gland Cells and Accelerates the Development of Primary Sjӧgren’s Syndrome in a Mouse Model

Jin¹,

Shinohara

Yu³

2013

PLoS ONE

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Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren’s syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues.

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Section: Introductionmentioning

confidence: 99%

Innate Immune Signaling Induces Interleukin-7 Production from Salivary Gland Cells and Accelerates the Development of Primary Sjӧgren’s Syndrome in a Mouse Model

Jin¹,

Shinohara

Yu³

2013

PLoS ONE

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“…Il17 −/− , B6J.NOD/ShiLtJ- Aec1Aec2 (B6.NOD- Aec1Aec2 ), B6.NOD- Aec1Aec2.Il17 −/ , and B6 mice were bred and maintained under specific pathogen free conditions in the animal facility of Animal Care Services at the University of Florida. Development and characterization of SjS-like phenotypic of the B6.NOD- Aec1Aec2 mouse are described elsewhere3261. Briefly, introduction of two genetic regions, one on chromosome 1 (designated Aec2 ) and the second on chromosome 3 (designated Aec1 ) derived from the NOD/LtJ mouse were bred into the B6 mouse.…”

Section: Methodsmentioning

confidence: 99%

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

Voigt

Esfandiary

Wanchoo

et al. 2016

Sci Rep

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Interleukin (IL)-17 is one of the critical inflammatory cytokines that plays a direct role in development of Sjögren’s syndrome (SjS), a systemic autoimmune disease characterized by a progressive chronic attack against the exocrine glands. The expression levels of IL-17 are correlated with a number of essential clinical parameters such as focus score and disease duration in human patients. Significantly immunological differences of Th17 cells were detected at the onset of clinical disease in female SjS mice compared to males. To further define the role of IL-17 in SjS and elucidate its involvement in the sexual dimorphism, we examined the systemic effect of IL-17 by genetically ablating Il-17 in the C57BL/6.NOD-Aec1Aec2, spontaneous SjS murine model. The results indicate that IL-17 is a potent inflammatory molecule in the induction of chemoattractants, cytokines, and glandular apoptosis in males and females. Elimination of IL-17 reduced sialadenitis more drastically in females than males. IL-17 is highly involved in modulating Th2 cytokines and altering autoantibody profiles which has a greater impact on changing plasma cells and germinal center B cell populations in females than males. The result supports a much more important role for IL-17 and demonstrates the sexual dimorphic function of IL-17 in SjS.

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“…These include (a) the potential impact of T1D on the physiological processes of saliva and tear secretion, (b) the probable interference of T1D on both overt and asymptomatic biological readouts in examining the underlying pathophysiological, biological and/or immunological pathology, (c) the inconsistent penetrance of diabetes in offspring, (d) the random requirement for insulin treatment, (e) the lack of a comparative non-disease control strain, and (f) the presence of a multitude of immune system-associated defects [44]. Construction of the C57BL/6.NOD- Aec1Aec2 mouse involved identification of two genetic regions ( Aec1 and Aec2 ) in the NOD mouse that not only showed synteny with genetic regions associated with SS, but proved necessary and sufficient to transfer SS-like disease to the non-autoimmune C57BL/6J mouse [27,28]. The C57BL/6J mouse was selected as the genetic background recipient strain, in part, because of the high number of single gene knock-out and knock-in transgenic mice being created in C57BL/6J mice making it possible to observe how individual genes alter the SS-like disease phenotype, even though this approach is totally artificial in comparison to the human disease.…”

Section: What Have We Learned About Ss From Mouse Models Of Ss-likmentioning

confidence: 99%

“…Nevertheless, genes of C57BL/6 mice residing outside of the Aec1 and Aec2 regions contribute significantly to the SS-like disease in C57BL/6.NOD- Aec1Aec2 mice [50]. For example, during the inflammatory and innate phases (correlating with the pre-clinical disease stage), there were no increases in the percent of genes up-regulated residing in the Aec1 and Aec2 genetic regions over genes not residing in these genetic regions, whereas in the autoimmune phase (correlating with overt clinical disease) the percent of genes in Aec1 and Aec2 up-regulated were significantly increased over genes residing outside these susceptibility regions [27,28, 38]. Thus, discrimination between disease-causing and disease-promoting genes becomes difficult to discriminate.…”

Section: What Have We Learned About Ss From Mouse Models Of Ss-likmentioning

confidence: 99%

What can Sjögren's syndrome-like disease in mice contribute to human Sjögren's syndrome?

Peck

Nguyen

2017

Clinical Immunology

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For decades, Sjögren’s syndrome (SS) and Sjögren’s syndrome-like (SS-like) disease in patients and mouse models, respectively, have been intensely investigated in attempts to identify the underlying etiologies, the path-ophysiological changes defining disease phenotypes, the nature of the autoimmune responses, and the propensity for developing B cell lymphomas. An emerging question is whether the generation of a multitude of mouse models and the data obtained from their studies is actually important to the understanding of the human disease and potential interventional therapies. In this brief report, we comment on how and why mouse models can stimulate interest in specific lines of research that apparently parallel aspects of human SS. Focusing on two mouse models, NOD and B6·Il14α, we present the possible relevance of mouse models to human SS, highlighting a few selected disease-associated biological processes that have baffled both SS and SS-like investigations for decades.

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IDD3 and IDD5 Alleles From Nod Mice Mediate Sjögren’s Syndrome-Like Autoimmunity

Cited by 10 publications

References 6 publications

Innate Immune Signaling Induces Interleukin-7 Production from Salivary Gland Cells and Accelerates the Development of Primary Sjӧgren’s Syndrome in a Mouse Model

Innate Immune Signaling Induces Interleukin-7 Production from Salivary Gland Cells and Accelerates the Development of Primary Sjӧgren’s Syndrome in a Mouse Model

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

What can Sjögren's syndrome-like disease in mice contribute to human Sjögren's syndrome?

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