Oxymatrine attenuates the type 1 diabetes mellitus via negative regulation of the follicular helper T cells

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which autoantibodies cause the immune system to attack and destroy pancreatic β-cells, leading to insufficient insulin production and impaired blood glucose control. T follicular helper (Tfh) cells are recognized as a group of CD4⁺ T cells that help B cells to produce high-affinity antibodies. Our previous research found that oxymatrine (OMT) exhibits excellent immunomodulatory properties on Tfh cells in autoimmune diseases. Based on the aforementioned research, we investigated whether OMT can modulate Tfh cells to reduce autoantibodies and thereby protect pancreatic β-cells in T1DM. Thus, we collected clinical laboratory examination indices from T1DM patients and utilized the well-known non-obese diabetic (NOD/LtJ) mouse model. Flow cytometry was used to detect changes in Tfh (CD4⁺CXCR5⁺ICOS⁺PD1⁺) cells, and the correlation between the Tfh cells percentage and serum factors was analyzed. We also measured changes in blood glucose, oral glucose tolerance, insulin, spleen germinal center, liver and kidney function, pancreatic and kidney tissues in NOD/LtJ mice. We found that in T1DM patients, the frequency of Tfh cells in peripheral blood was increased and positively correlated with elevated levels of autoantibodies and serum cytokines. After OMT treatment, NOD/LtJ mice showed increased serum insulin levels, protection of pancreatic and kidney tissues, and a significant control of Tfh cells expansion in the spleen. In summary, OMT may have therapeutic effects on type 1 diabetes mellitus via negatively regulating T follicular helper cells to protect pancreatic islets β cells.