In Vivo Generation of SSA/Ro Antigen-Specific Regulatory T Cells Improves Experimental Sjögren's Syndrome in Mice.
In Vivo Generation of SSA/Ro Antigen-Specific Regulatory T Cells Improves Experimental Sjögren's Syndrome in Mice.
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DOI：
10.1002/art.42244
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发表时间：
2022-10
影响因子：
13.3
通讯作者：
Chen, WanJun
中科院分区：
文献类型：
--
作者：
Xu, Junji;Liu, Ousheng;Wang, Dandan;Wang, Fu;Zhang, Dunfang;Jin, Wenwen;Cain, Alexander;Bynum, Andrew;Liu, Na;Han, Yichen;Chen, WanJun
Sjögren综合征（SS）是一种全身性自身免疫性疾病，T细胞在疾病的发生和延续中起着重要作用。在这里，我们开发了一种针对ss样NOD/Ltj小鼠的免疫疗法，通过将CD4+ T细胞的短暂消耗与自身抗原特异性肽Ro480的管理结合起来。NOD/Ltj小鼠接受单抗cd4单抗治疗，2天后每隔一天连续注射Ro480-494 6次。每周一次测定治疗前后的唾液流量。初始抗cd4单抗治疗6周后处死小鼠，收集唾腺（SG）进行组织学疾病评分和炎症细胞浸润分析，PCR检测基因，流式细胞术分析包括免疫细胞MHC II类四聚体染色。此外，还采用过继性转移Treg来研究体内新生成Treg的功能。抗CD4单抗与自身抗原特异性肽Ro480联合在体内产生SSA/ ro抗原特异性Tregs，可抑制CD4+ T细胞IFN-γ的产生和SG的炎症浸润，维持SG的功能。我们的发现提供了一种在体内产生抗原特异性Tregs治疗SS的新方法，这应该对SS患者的潜在治疗具有指导意义。
Sjögren’s syndrome (SS) is a systemic autoimmune disease and T cells play an important role in the initiation and perpetuation of the disease. Here, we developed an immunotherapy for SS-like NOD/Ltj mice by combining a transient depletion of CD4+ T cells together with the administration of autoantigen-specific peptide Ro480. NOD/Ltj mice were treated with single anti-CD4 mAb followed 2 days later by a series of 6 injections (i.p.) of Ro480–494 every other day. Salivary flow rates were determined pre- and post-treatment once a week. Mice were sacrificed 6 weeks post initial anti-CD4 mAb treatment, salivary glands (SG) were collected for analyses of histological disease scores and inflammatory cell infiltration, PCR determination of genes and flow cytometry analysis including MHC class II tetramer staining of immune cells. In addition, adoptive transferring of Tregs was administrated to investigate the function of the newly generating Treg in vivo. The combination of anti-CD4 mAb with autoantigen-specific peptide Ro480 generates SSA/Ro-antigen specific Tregs in vivo, which can suppress IFN-γ production of CD4+ T cells and the inflammation infiltration in SG, and maintain the function of SG. Our findings provide a new approach to generating antigen-specific Tregs in vivo for SS treatment, which should have implications for potential therapy for patients with SS.
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影响因子：
17.1
作者：
Kasagi, Shimpei;Zhang, Pin;Chen, WanJun
通讯作者：
Chen, WanJun
影响因子：
15.9
作者：
Rep, MHG;vanOosten, BW;vanLier, RAW
通讯作者：
vanLier, RAW
影响因子：
6
作者：
Christodoulou, Maria I.;Kapsogeorgou, Efstathia K.;Moutsopoulos, Haralampos M.
通讯作者：
Moutsopoulos, Haralampos M.
DOI：
10.1084/jem.20030152
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen W;Jin W;Hardegen N;Lei KJ;Li L;Marinos N;McGrady G;Wahl SM
通讯作者：
Wahl SM
影响因子：
82.9
作者：
Perruche, Sylvain;Zhang, Pin;Chen, WanJun
通讯作者：
Chen, WanJun