Xue Jinmei, Suo Limin, An Yunfang, Wang Xinxin, Zhang Shuang, Liu Huazhen, Wu Yongjin, Sun Xizhuo, Zhao Changqing, Yang Pingchang
Department of Otolaryngology, Head & Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, China.
Guangdong Provincial Regional Disease Key Laboratory, Shenzhen, China; Institute of Allergy & Immunology, Shenzhen University School of Medicine, State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University, Shenzhen, China.
Immunol Lett. 2023 Dec;264:46-55. doi: 10.1016/j.imlet.2023.11.006. Epub 2023 Nov 24.
Type 1 regulatory T cells (Tr1 cells) play an important role in the maintenance of the immune homeostasis in the body. The induction of Tr1 cell is to be further investigated. The interaction of phosphatidylserine (PS) with TIM3 has immune regulation functions. The objective of this study is to elucidate the role of PS-TIM3 signals in inducing Tr1 cells. In this study, mice were treated using PS or specific immunotherapy by nasal instillation. A murine model of allergic rhinitis was developed using ovalbumin as a specific antigen. We found that PS-containing nasal instillation induced Tr1 cells in the airway tissues. PS promoted gene activities associated with IL-10 through activation of TIM3 in CD4 T cells. TIM3 mediated the effects of PS on inducing Tr1 cells, in which the TIM3- PI3K-AKT pathway played a critical role. PS boosted allergen-specific immunotherapy by inducing specific antigen Tr1 cell generation. Concomitant administration of PS and SIT resulted in better therapeutic effects on AR. In conclusion, the data demonstrate that PS can promote the specific immunotherapy for AR through inducing antigen specific Tr1 cells in the airway tissues.
1型调节性T细胞（Tr1细胞）在维持机体免疫稳态中发挥重要作用。Tr1细胞的诱导机制有待进一步研究。磷脂酰丝氨酸（PS）与TIM3的相互作用具有免疫调节功能。本研究旨在阐明PS-TIM3信号在诱导Tr1细胞中的作用。在本研究中，通过滴鼻给予PS或特异性免疫疗法处理小鼠。以卵清蛋白作为特异性抗原建立变应性鼻炎小鼠模型。我们发现含PS的滴鼻剂可诱导气道组织中的Tr1细胞。PS通过激活CD4 T细胞中的TIM3促进与IL-10相关的基因活性。TIM3介导PS诱导Tr1细胞的作用，其中TIM3-PI3K-AKT途径起关键作用。PS通过诱导特异性抗原Tr1细胞生成增强变应原特异性免疫疗法。PS与特异性免疫疗法联合应用对变应性鼻炎具有更好的治疗效果。总之，数据表明PS可通过诱导气道组织中抗原特异性Tr1细胞促进变应性鼻炎的特异性免疫治疗。
