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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (6): 783-794    DOI: 10.3724/zdxbyxb-2021-0072
    
Research progress on inflammatory mechanism of primary Sj?gren syndrome
REN Yuan,CUI Gedan,GAO Yongxiang()
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
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Abstract  

Primary Sj?gren syndrome is an autoimmune disease, in which a large number of lymphocytes infiltrate the exocrine glands and cause gland dysfunction. Its pathogenesis is related to the chronic inflammation of the exocrine glands caused by genetic factors, immunodeficiency or viral infection. Long-term inflammation leads to accelerated apoptosis of epithelial cells, disordered gland structure, increased expression of proinflammatory cytokine such as CXC subfamily ligand (CXCL) 12, CXCL13, B cell-activating factor (BAF), interleukin (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α in submandibular gland. With the action of antigen-presenting cells such as dendritic cells and macrophages, lymphocytes (mainly B cells) are induced to mature in secondary lymphoid organs and migrate to the submandibular gland to promotes the formation of germinal centers and the synthesis of autoantibodies. Meanwhile, innate lymphocytes, vascular endothelial cells and mucosa-associated constant T cells as important immune cells, also participated in the inflammatory response of the submandibular gland in primary Sj?gren syndrome through different mechanisms. This process involves the activation of multiple signal pathways such as JAK/STAT, MAPK/ERK, PI3K/AKT/mTOR, PD-1/PD-L1, TLR/MyD88/NF-κB, BAF/BAF-R and IFN. These signaling pathways interact with each other and are intricately complex, causing lymphocytes to continuously activate and invade the submandibular glands. This article reviews the latest literature to clarify the mechanism of submandibular gland inflammation in primary Sj?gren syndrome, and to provide insights for further research.



Key wordsPrimary Sj?gren syndrome      Submandibular gland      Immunocytes      Inflammatory response mechanisms      Signaling pathway      Review     
Received: 16 March 2021      Published: 22 March 2022
CLC:  R593.2  
Corresponding Authors: GAO Yongxiang     E-mail: drgaoyx@cdutcm.edu.cn
Cite this article:

REN Yuan,CUI Gedan,GAO Yongxiang. Research progress on inflammatory mechanism of primary Sj?gren syndrome. J Zhejiang Univ (Med Sci), 2021, 50(6): 783-794.

URL:

https://www.zjujournals.com/med/10.3724/zdxbyxb-2021-0072     OR     https://www.zjujournals.com/med/Y2021/V50/I6/783


原发性干燥综合征患者颌下腺炎症反应机制研究进展

原发性干燥综合征是一种由大量淋巴细胞浸润外分泌腺并导致腺体功能障碍的自身免疫性疾病,其发病机制与遗传、免疫缺陷和病毒感染等导致外分泌腺慢性炎症反应有关。长期炎症使颌下腺上皮细胞凋亡加快,腺体结构紊乱,趋化因子CXC亚家族配体(CXCL)12和CXCL13、B细胞活化因子(BAF)、白介素-6、γ干扰素和肿瘤坏死因子α等炎症因子表达增加,在树突状细胞、巨噬细胞等抗原呈递细胞的作用下,诱导以B淋巴细胞为主的淋巴细胞在次级淋巴器官中成熟并迁徙至颌下腺,促进生发中心的形成和自身抗体的合成。同时,先天淋巴细胞、血管内皮细胞及黏膜相关恒定T细胞作为重要的免疫细胞,也通过不同作用机制参与了原发性干燥综合征患者颌下腺的炎症反应。这个过程涉及JAK激酶/信号转导及转录激活蛋白、丝裂原激活蛋白激酶/胞外信号调节激酶、磷酸酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白、程序性死亡蛋白1/程序性死亡蛋白配体1、Toll样受体/髓样分化因子88/核因子κB、BAF/BAF受体以及干扰素等多条信号通路的激活,这些信号通路相互影响,错综复杂,导致淋巴细胞不断活化并侵袭颌下腺。本文对国内外最新研究进行了综述,以期阐明原发性干燥综合征患者颌下腺炎症反应的机制,为下一步研究提供思路。


关键词: 原发性干燥综合征,  颌下腺,  免疫细胞,  炎症机制,  信号通路,  综述 
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