Mechanism of IL-17 in breaking the tolerance induced by MBP via nasal mucosa in EAE model

ZHANG Yao; MENG Qingfeng; WANG Jinghua; SUN Bo; KONG Qingfei; LIU Yumei; ZHOU Mingyan; LIU Xijun; LI Hulun; WANG Guangyou

Abstract：Objective To investigate the mechanism of IL-17 in breaking the tolerance induced by peptide MBP68-86 via nasal mu-cosa in EAE model.Four groups of lewis rats were given with PBS, MBP, MBP+IL-17 (via nasal mucosa), and MBP+IL-17 (via nasal mucosa) with anti-IL-6 (peritoneal injection), respectively.After five days administration for immune tolerance, the model of EAE was established.ELISA was employed to detect the levels of cytokines IFN-γ, IL-4, IL-6, IL-17, and TGF-β, which were significant difference between IL-17 group and MBP group (P< 0.05, P< 0.01, P< 0.01, P< 0.001, P< 0.01, respectively), but no significance between IL-17 group and PBS group.As compared with MBP and MBP+IL-17 with anti-IL-6 peritoneal injection group, body weight loss, tail paralysis, posterior limb paralysis were observed in MBP+IL-17 and PBS group after immunization.HE staining showed the area of lymphocyte infiltration were large, and the quantity of IL-17~+ cells was significantly increased in spinal cord section of MBP+IL-17 and PBS group rats; Immunohistochemical method demonstrated that the percentage of CD4~+IL-17~+T cells increased significantly while CD4~+Foxp3~+T cells was noticeable reduced in lymph nodes of MBP+IL-17 and PBS group rats.All the results mean that IL-17 administration via nasal mucosa can break the MBP-induced tolerance by increasing the expression of IL-6, which makes the increasing differentiation from naive T cell to Th17 cell.