Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice.
Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice.
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DOI：
10.3390/ijms21249478
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发表时间：
2020-12-13
影响因子：
5.6
通讯作者：
Lieberman SM
中科院分区：
文献类型：
--
作者：
Debreceni IL;Chimenti MS;Serreze DV;Geurts AM;Chen YG;Lieberman SM
干燥综合征（SS）是一种免疫学复杂的慢性自身免疫性疾病，靶向泪腺和唾液腺。非肥胖型糖尿病（NOD）小鼠自发发生泪腺和唾液腺炎症，其组织病理学特征与人类SS相似，包括受影响腺体中的局灶性淋巴细胞浸润。驱动淋巴细胞浸润这些腺体的先天性免疫信号尚未明确。在这里，我们评估Toll样受体（TLR）7在NOD小鼠SS样表现的发展中的作用。我们建立了一个TLR7基因敲除NOD小鼠品系，并进行了组织学和基因表达研究，以表征TLR7对自身免疫发展的影响。TLR7是男性特异性泪腺炎症所必需的，但不是女性特异性唾液腺炎症所必需的。此外，TLR7是雄性NOD小鼠而非雌性NOD小鼠发生1型糖尿病所必需的。RNA测序证实，TLR7与泪腺中的I型干扰素（IFN）应答和I型IFN非依赖性B细胞应答相关。这些研究共同确定了TLR7在雄性NOD小鼠泪腺自身免疫和T1D发展中的先前未被认识到的致病作用，增加了越来越多的证据支持NOD小鼠自身免疫性疾病机制的性别差异。
Sjögren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.
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影响因子：
5.6
作者：
Chaly Y;Barr JY;Sullivan DA;Thomas HE;Brodnicki TC;Lieberman SM
通讯作者：
Lieberman SM
影响因子：
8.8
作者：
Ciecko, Ashley E.;Foda, Bardees;Chen, Yi-Guang
通讯作者：
Chen, Yi-Guang
影响因子：
7.7
作者：
Carrero, Javier A.;Benshoff, Nicholas D.;Unanue, Emil R.
通讯作者：
Unanue, Emil R.
影响因子：
15.9
作者：
Hunger, RE;Carnaud, C;Mueller, C
通讯作者：
Mueller, C
影响因子：
7
作者：
Draghici, Sorin;Khatri, Purvesh;Romero, Roberto
通讯作者：
Romero, Roberto