二甲双胍诱导的Ca2+信号激活可防止干燥综合征易发小鼠模型的免疫浸润/病理

IF 4.7 Q2 IMMUNOLOGY
Viviane Nascimento Da Conceicao , Yuyang Sun , Xiufang Chai , Julian L. Ambrus , Bibhuti B. Mishra , Brij B. Singh
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引用次数: 0

摘要

免疫细胞浸润和腺体功能障碍是原发性干燥综合征(pSS)等自身免疫性疾病的标志,但其机制尚不清楚。我们的数据表明,二甲双胍处理诱导Ca2+信号,恢复唾液分泌,阻止免疫细胞浸润IL14α-转基因小鼠(IL14α)的唾液腺,这是pSS的模型。在机制上,我们发现Ca2+信号的丢失是一个主要的促成因素,在IL14α小鼠中通过二甲双胍治疗恢复。此外,Ca2+信号的丢失导致唾液腺内质网应激。最后,二甲双胍诱导的Ca2+信号的恢复抑制了警报的释放,并阻止了免疫细胞浸润所必需的内质网应激的激活。这些结果表明,二甲双胍介导的Ca2+信号激活的丧失可以阻止内质网应激,从而抑制诱发免疫细胞浸润的警报器的释放,从而导致pSS中观察到的唾液腺功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metformin-induced activation of Ca2+ signaling prevents immune infiltration/pathology in Sjogren’s syndrome-prone mouse models

Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren’s syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces Ca2+ signaling that restores saliva secretion and prevents immune cell infiltration in the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of Ca2+ signaling is a major contributing factor, which is restored by metformin treatment, in IL14α mice. Furthermore, the loss of Ca2+ signaling leads to ER stress in salivary glands. Finally, restoration of metformin-induced Ca2+ signaling inhibited the release of alarmins and prevented the activation of ER stress that was essential for immune cell infiltration. These results suggest that loss of metformin-mediated activation of Ca2+ signaling prevents ER stress, which inhibited the release of alarmins that induces immune cell infiltration leading to salivary gland dysfunction observed in pSS.

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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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