Cong Yan, Tang Xiaojun, Wang Dandan, Zhang Zhuoya, Huang Saisai, Zhang Xin, Yao Genhong, Sun Lingyun
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Rheumatology and Immunology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, China.
Ann Transl Med. 2022 May;10(10):594. doi: 10.21037/atm-22-1855.
Since gamma delta (γδ) T cells are involved in various autoimmune diseases, we aimed to verify whether γδ T cells participate in the pathogenesis of Sjögren's syndrome (SS) and related pulmonary inflammation, and also aimed to evaluate the effects of umbilical cord mesenchymal stem cells (MSCs) on SS-related pulmonary inflammation and the γδ T cells.
The saliva flow rates of female non-obese diabetic (NOD/Ltj) mice were measured. Histopathologic analysis was performed in salivary glands (SG) and lung tissues. The levels of γδ T cells and their subsets in the peripheral blood, spleen, and lung were examined by flow cytometry. The purified γδ T cells were adoptively transferred into NOD/Ltj mice. MSC transplantation was performed in 8-week-old NOD/Ltj mice.
The results showed lymphocytic infiltration in SG and lacrimal glands (LG), and reduction of saliva flow rates in 8-week NOD/Ltj mice. The levels of γδ T cells decreased in peripheral blood, but increased in the lung of 8- and 12-week-old NOD/Ltj mice. The proportions and numbers of Vγ4 T cells and Vγ4 IL-17A T cells increased in the lung, but decreased in peripheral blood of 8-week-old NOD/Ltj mice. Notably, transfer of γδ T cells decreased the rate of saliva flow, as well as aggravated the pathological changes in the lung. The transplantation of MSCs increased saliva flow rate and alleviated pathological injury in the SG and lung. The frequencies of Vγ4 T cells and Vγ4 IL-17A T cells in the lung and spleen significantly decreased after MSC treatment. Our results demonstrated that γδ T cells and Vγ4+ T cells contribute to the pathogenesis of SS and SS-related pulmonary inflammation. In addition, MSCs relieved SS and SS-related pulmonary inflammation through suppressing Vγ4 IL-17A T cells.
Peripheral Vγ4 T cells infiltrate into the lung in SS mice, and aggravate the symptoms of SS and SS-related pulmonary inflammation by secreting IL-17A. Meanwhile, lymphocyte infiltration could be reversed by MSC transplantation, which indicates the potential of MSCs in the treatment of SS and SS-related pulmonary inflammation patients.
由于γδ T细胞参与多种自身免疫性疾病，我们旨在验证γδ T细胞是否参与干燥综合征（SS）的发病机制及相关肺部炎症，同时评估脐带间充质干细胞（MSCs）对SS相关肺部炎症及γδ T细胞的影响。
测量雌性非肥胖糖尿病（NOD/Ltj）小鼠的唾液流速。对唾液腺（SG）和肺组织进行组织病理学分析。通过流式细胞术检测外周血、脾脏和肺中γδ T细胞及其亚群的水平。将纯化的γδ T细胞过继转移到NOD/Ltj小鼠体内。对8周龄的NOD/Ltj小鼠进行MSC移植。
结果显示8周龄NOD/Ltj小鼠的SG和泪腺（LG）有淋巴细胞浸润，唾液流速降低。外周血中γδ T细胞水平降低，但8周龄和12周龄NOD/Ltj小鼠肺中的γδ T细胞水平升高。8周龄NOD/Ltj小鼠肺中Vγ4 T细胞和Vγ4 IL-17A T细胞的比例和数量增加，但外周血中减少。值得注意的是，γδ T细胞的转移降低了唾液流速，并加重了肺部的病理变化。MSC移植增加了唾液流速，减轻了SG和肺的病理损伤。MSC治疗后，肺和脾脏中Vγ4 T细胞和Vγ4 IL-17A T细胞的频率显著降低。我们的结果表明，γδ T细胞和Vγ4 + T细胞参与SS及SS相关肺部炎症的发病机制。此外，MSCs通过抑制Vγ4 IL-17A T细胞减轻SS及SS相关肺部炎症。
外周Vγ4 T细胞在SS小鼠中浸润到肺中，并通过分泌IL-17A加重SS及SS相关肺部炎症的症状。同时，MSC移植可逆转淋巴细胞浸润，这表明MSCs在治疗SS及SS相关肺部炎症患者方面具有潜力。
