New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland

Kayes, Timothy; Weisman, Gary A.; Camden, Jean M.; Woods, Lucas T.; Bredehoeft, Cole; Downey, Edward F.; Cole, James H.; Braley‐Mullen, Helen

doi:10.4049/jimmunol.1600133

Cited by 13 publications

(26 citation statements)

References 64 publications

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“…A third point to take into account is the existence of animal models that spontaneously develop both SS and AITD. Thyroiditis and SS in NOD.H-2h4 mice are chronic autoimmune diseases that develop relatively early in life and persist for the life of the animal making them an excellent model to test therapeutic protocols over a long period of time ( 44 ).…”

Section: Introductionmentioning

confidence: 99%

The Association of Sjögren Syndrome and Autoimmune Thyroid Disorders

et al. 2018

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Sjögren’s syndrome (SS) and autoimmune thyroid diseases (AITD) may frequently coexist in clinical practice, resulting in a complex overlapping disorder that represents a particular example of the expression of heterogeneity in patients with autoimmune disorders. Objective of this review was to describe the prevalence of the SS–AITD association in the most recent literature, exploring in particular to what extent the presence of AITD might influence the clinical expression of SS and vice versa. Moreover, we summarized some of the proposed genetic, biologic, and molecular mechanisms implied in the pathogenesis of AITD–SS association. Finally, we explored risk factors for lymphoma development in both AITD and SS. We performed a Medline search of English language articles published in the PubMed database in order to provide a critical overview of the recent literature on pathogenesis and clinical features of AITD–SS overlapping disease. All the articles were critically analyzed to select the most relevant contributions.

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Section: Introductionmentioning

confidence: 99%

The Association of Sjögren Syndrome and Autoimmune Thyroid Disorders

et al. 2018

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“…ATD in IFN-γ −/− mice is a T cell–dependent autoimmune disease in which activated autoreactive CD4 + and CD8 + T cells migrate to the thyroid where they produce TNF-α and other cytokines that act on thyrocytes to promote their proliferation (7). Because severe ATD develops slowly and in only 60–70% of IFN-γ −/− NOD.H-2h4 mice, we generated CD28-deficient IFN-γ −/− NOD.H-2h4 mutants that develop severe ATD and hypothyroid-ism, with a nearly 100% incidence at 4 mo of age (1, 8). Female CD28 −/− mice also develop more severe pSS than WT NOD.H-2h4 mice (1, 8).…”

Section: Introductionmentioning

confidence: 99%

“…Because severe ATD develops slowly and in only 60–70% of IFN-γ −/− NOD.H-2h4 mice, we generated CD28-deficient IFN-γ −/− NOD.H-2h4 mutants that develop severe ATD and hypothyroid-ism, with a nearly 100% incidence at 4 mo of age (1, 8). Female CD28 −/− mice also develop more severe pSS than WT NOD.H-2h4 mice (1, 8). As shown by us (4) and other investigators (2, 9, 10), pSS is also a T cell–dependent autoimmune disease with activated CD4 + and CD8 + T cells and B cells in the salivary gland infiltrates and, like ATD, proinflammatory cytokine production by T cells likely mediates the damage to the organ.…”

Section: Introductionmentioning

confidence: 99%

“…Blocking or elimination of the B7: CD28 or PD-1/PDL pathway can result in development of autoimmunity (27, 28). CD28 −/− mice develop autoimmunity as a result of the absence of most functional regulatory T cells (Tregs) (8, 13, 29, 30), whereas autoimmunity in PD-1 −/− mice develops as a result of the loss of an important inhibitory pathway (31).…”

Section: Introductionmentioning

confidence: 99%

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Requirement for CD40/CD40L Interactions for Development of Autoimmunity Differs Depending on Specific Checkpoint and Costimulatory Pathways

Voynova¹,

Mahmoud²,

Woods

et al. 2018

ImmunoHorizons

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CD40/CD40L interactions play a critical role in immunity and autoimmunity. In this study, we sought to understand the requirement for CD40 signaling in the programmed cell death-1 (PD-1) checkpoint and CD28 costimulatory pathways important for maintenance of peripheral tolerance. Blocking either pathway can result in loss of self-tolerance and development of autoimmunity. We found that primary Sjögren’s syndrome (pSS) and autoimmune thyroid diseases (ATDs) that develop spontaneously in CD28-deficient IFN-γ −/− NOD.H-2h4 (CD28 −/− ) mice required CD40 signaling. Specifically, blockade of CD40L with the anti-CD40L mAb, MR1, inhibited autoantibody production and inflammation in thyroid and salivary gland target tissues. Unexpectedly, however, ATD and pSS in PD-1–deficient IFN-γ −/− NOD.H-2h4 (PD-1 −/− ) mice developed independently of CD40/CD40L interactions. Treatment with MR1 had no effect and even exacerbated disease development in pSS and ATD, respectively. Most interesting, anti-thyroglobulin and pSS-associated autoantibodies were increased following anti-CD40L treatment, even though MR1 effectively inhibited the spontaneous splenic germinal centers that form in PD-1–deficient mice. Importantly, blockade of the PD-1 pathway by administration of anti–PD-1 mAb in CD28 −/− mice recapitulated the PD-1 −/− phenotype, significantly impacting the ability of MR1 to suppress ATD and pSS in these mice. These results indicate that there can be different pathways and requirements to autoimmune pathogenesis depending on the availability of specific checkpoint and costimulatory receptors, and an intact PD-1 pathway is apparently required for inhibition of autoimmunity by anti-CD40L.

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“…The salivary glands, like thyroids, are able to concentrate iodide so its salivary concentration is from 20 to 100 times more than that found in the serum. This glandular critical ability could cause damage, like cellular infiltration, in this extrathyroid tissue [ 14 , 15 ]. Lymphocyte accumulation in salivary glands represents one of the leading causes of dry eye and mouth in the world, with these symptoms being also related to Sjogren syndrome, a systemic chronic autoimmune disease that targets predominantly the salivary glands and lacrimal glands [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Excess Iodide Intake on Salivary Glands in a Swiss Albino Mice Model

Ross

Fabersani

Russo

et al. 2017

BioMed Research International

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Iodine is an important micronutrient required for nutrition. Excess iodine has adverse effects on thyroid, but there is not enough information regarding its effect on salivary glands. In addition to food and iodized salt, skin disinfectants and maternal nutritional supplements contain iodide, so its intake could be excessive during pregnancy, lactation, and infancy. The aim of this work was to evaluate the effect of excess iodide ingestion on salivary glands during mating, gestation, lactation, and postweaning period in mouse. During assay, mice were allocated into groups: control and treatment groups (received distilled water with NaI 1 mg/mL). Water intake, glandular weight, and histology were analyzed. Treatment groups showed an increase in glandular weight and a significantly (p < 0.05) higher water intake than control groups. Lymphocyte infiltration was observed in animals of treatment groups, while there was no infiltration in glandular sections of control groups. Results demonstrated that a negative relationship could exist between iodide excess and salivary glands. This work is novel evidence that high levels of iodide intake could induce mononuclear infiltration in salivary glands. These results should be considered, especially in pregnant/lactating women, to whom a higher iodine intake is usually recommended.

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New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland

Cited by 13 publications

References 64 publications

The Association of Sjögren Syndrome and Autoimmune Thyroid Disorders

The Association of Sjögren Syndrome and Autoimmune Thyroid Disorders

Requirement for CD40/CD40L Interactions for Development of Autoimmunity Differs Depending on Specific Checkpoint and Costimulatory Pathways

Effect of Excess Iodide Intake on Salivary Glands in a Swiss Albino Mice Model

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