Umbilical cord mesenchymal stem cells alleviate Sj?gren?s syndrome and related pulmonary inflammation through regulating V?4+IL-17+T cells

Background: Since gamma delta (gamma delta) T cells are involved in various autoimmune diseases, we aimed to verify whether gamma delta T cells participate in the pathogenesis of Sjogren'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 gamma delta T cells. Methods: 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 gamma delta T cells and their subsets in the peripheral blood, spleen, and lung were examined by flow cytometry. The purified gamma delta T cells were adoptively transferred into NOD/Ltj mice. MSC transplantation was performed in 8-week-old NOD/Ltj mice. Results: 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 gamma delta T cells decreased in peripheral blood, but increased in the lung and spleen of 8- and 12-week-old NOD/Ltj mice. The proportions and numbers of V gamma 4+ T cells and V gamma 4+ IL-17A+ T cells increased in the lung, but decreased in peripheral blood of 8-week-old NOD/Ltj mice. Notably, transfer of gamma delta T cells decreased the rate of saliva flow, as well as aggravated the pathological changes in the SG and lung. The transplantation of MSCs increased saliva flow rate and alleviated pathological injury in the SG and lung. The frequencies of V gamma 4+ T cells and V gamma 4+ IL-17A+ T cells in the lung and spleen significantly decreased after MSC treatment. Our results demonstrated that gamma delta T cells and their subsets contribute to the pathogenesis of SS and SS-related pulmonary inflammation. In addition, MSCs relieved SS and SS-related pulmonary inflammation through suppressing V gamma 4+ IL-17A+ T cells. Conclusions: Peripheral V gamma 4+ 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