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淋巴细胞特异性蛋白1(LSP1)缺陷会增加表达白细胞介素-17(IL-17)的T细胞,并加速原发性干燥综合征的发展。

LSP1 deficiency increases IL-17-expressing T cells and accelerates primary Sjögren's syndrome.

作者信息

Kim Jayhyun, Kim Jung Gon, Li Yingjin, You Sungyong, Lee Naeun, Kim Wan-Uk

机构信息

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea; Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea.

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea; Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea.

出版信息

Clin Immunol. 2025 Nov;280:110548. doi: 10.1016/j.clim.2025.110548. Epub 2025 Jun 28.

Abstract

Lymphocyte-specific protein-1 (LSP1) is known to negatively regulate T cell migration in autoimmune diseases. However, its role in the development of T cell-dependent Sjögren's syndrome remains unknown. In this study, we found that LSP1 expression was decreased in T cells in salivary glands (SGs) of mice with experimental Sjögren's syndrome, accompanied by enhanced infiltration of leukocytes into SGs. Moreover, Lsp1 mice had higher frequency of IL-17A-expressing T cells in cervical lymph nodes as well as increased severity in SGs than WT mice. Concurrently, LSP1 expression was reduced in human T cells of primary Sjögren's syndrome (pSS) patient. Particularly, pSS patients showed an increased Th17 cells, which inversely correlated with LSP1 expression. Taken together, these findings suggest that LSP1 deficiency promote Th17 cell development and exacerbation of pSS. LSP1 might be a potential therapeutic target to regulate Th17 response and to treat autoimmune diseases like pSS.

摘要

已知淋巴细胞特异性蛋白-1(LSP1)在自身免疫性疾病中对T细胞迁移起负调控作用。然而,其在T细胞依赖性干燥综合征发展中的作用尚不清楚。在本研究中,我们发现实验性干燥综合征小鼠唾液腺(SGs)中的T细胞中LSP1表达降低,同时白细胞向SGs的浸润增强。此外,与野生型小鼠相比,Lsp1小鼠颈部淋巴结中表达IL-17A的T细胞频率更高,SGs中的严重程度也增加。同时,原发性干燥综合征(pSS)患者的人T细胞中LSP1表达降低。特别是,pSS患者的Th17细胞增加,这与LSP1表达呈负相关。综上所述,这些发现表明LSP1缺乏促进Th17细胞发育和pSS病情加重。LSP1可能是调节Th17反应和治疗pSS等自身免疫性疾病的潜在治疗靶点。

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