Th17 Cell Roles In Pathogenesis Of Experimental Autoimmune Myasthenia Gravis

Objective:To investigate the role of Th17 cells and its correlation cytokine IL-17 in the pathogenesis of experimental autoimmune myasthenia gravis(EAMG).Methods:The CCL2-deficient (CCL2-/-) mice and C57BL/6 (B6) mice model of EAMG were established by injecting Acetylcholine receptors (AChR), clinical evaluation the mice of EAMG according to severity of clinical symptoms.Antibody level of blood serum was detected by ELISA, for CD4+IL-17+ lymphocytes,CD4+ IFN-?+ lymphocytes and CD4+IL-4+ lymphocytes content by flow cytometry.Results:1.CCL2-/- mice was not observed the phenomenon of muscular weakness.The level of serum anti AChR IgGl and IgG2a in CCL2-/- mice is similar to that of B6 mice,but IgG2b level is significantly reduced compare to that of B6 mice.2. Separating T lymphocytes from CCL2-/- mice and B6 mice, the number of CD4+T cells that secretes IFN-?(Th1 cell) and IL-4(Th2 cell) in CCL2-/- mice is slightly less than that of B6 mice,but the number of CD4+T cells that secretes IL-17 cells is significantly reduced in CCL2-/- mice than that of B6 mice.3. In B6 mice, exogenous administration of IL-17 were injected to the test team,using PBS as control,the test team developed severe muscular weakness and high level of specific anti AChR IgG2b, the test team showed significantly difference with those in control team.In CCL2-/- mice, exogenous administration of IL-17 were injected to the test team,using PBS as control, the test team develop muscular weakness very early and gradually increasing weakness and high level of specific anti AChR IgG2b, the test team showed significantly difference with those in control team.Conclusions:The Th17 cells and its correlation cytokine IL-17 are required as helpers for the production of high titer of pathogenic anti-AChR IgG2b antibodies from B cells. Those antibodies are the ultimate responsible for the block at the neuromuscular junction that leads to muscular weakness.