Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome.
Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome.
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DOI：
10.3390/ijms19103259
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发表时间：
2018-10-20
影响因子：
5.6
通讯作者：
Lieberman SM
中科院分区：
文献类型：
--
作者：
Chaly Y;Barr JY;Sullivan DA;Thomas HE;Brodnicki TC;Lieberman SM
非肥胖型糖尿病（NOD）小鼠自发产生泪腺和唾液腺自身免疫，类似于人类干燥综合征。在人类和NOD小鼠中，驱动T细胞浸润到泪腺和唾液腺中的早期免疫应答知之甚少。在NOD小鼠中，泪腺自身免疫仅自发地发生在雄性中，睾酮在促进泪腺炎症中起作用，而雌性泪腺受调节性T细胞（T细胞）保护。这种男性特有的泪腺自身免疫的机制尚不清楚。在这里，我们研究了Treg耗竭对泪腺基因表达的影响，以确定泪腺炎症所需的早期信号。虽然Treg耗竭不足以驱动去势雄性NOD小鼠的泪腺炎，但趋化因子（Cxcl 9，Ccl 19）和其他潜在的疾病相关基因（Epsti 1，Ubd）在雄性泪腺中上调。Cxcl 9和Ccl 19的表达，特别是，在淋巴细胞缺陷型NOD-严重联合免疫缺陷（SCID）小鼠的泪腺中保持显著上调，并且它们的表达受到I型干扰素信号转导的调节。值得注意的是，Ifnar 1缺陷型NOD小鼠没有发生泪腺炎。这些数据共同鉴定了在男性特异性泪腺炎背景下上调的疾病相关基因，并证明了NOD小鼠泪腺自身免疫中I型干扰素信号传导的必要作用。
Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (Cxcl9, Ccl19) and other potentially disease-relevant genes (Epsti1, Ubd) were upregulated in male lacrimal glands. Expression of Cxcl9 and Ccl19, in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, Ifnar1-deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.
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影响因子：
4.6
作者：
Nguyen NT;Now H;Kim WJ;Kim N;Yoo JY
通讯作者：
Yoo JY
影响因子：
3.7
作者：
Jin, Jun-O;Shinohara, Yoshinori;Yu, Qing
通讯作者：
Yu, Qing
DOI：
10.1016/j.bbrc.2017.12.014
发表时间：
2018-02-05
影响因子：
3.1
作者：
Kim, Young-Hoon;Lee, Jae-Rin;Hahn, Myong-Joon
通讯作者：
Hahn, Myong-Joon
影响因子：
4.9
作者：
Raterman HG;Vosslamber S;de Ridder S;Nurmohamed MT;Lems WF;Boers M;van de Wiel M;Dijkmans BA;Verweij CL;Voskuyl AE
通讯作者：
Voskuyl AE
影响因子：
5.3
作者：
Canaan, Allon;Yu, Xiaofeng;Weissman, Sherman M.
通讯作者：
Weissman, Sherman M.