Abstract: Objective To investigate the activities of Treg cells and the expression of MOF in the peak and remission periods of experimental allergic encephalomyelitis(EAE)mice and the impact of MOF on the pathogenesis of EAE. Methods On Day 0, twenty 6-8 week old C57BL/6 female mice of similar weight were subcutaneously injected with 200 μg MOG_35-55 or complete freunds adjuvant(CFA)and then intraperitoneally injected with 200 ng pertussis toxin. On Day 2, the above three mice were intraperitoneally injected with 200 ng pertussis toxin. The spleen tissues of the EAE mice in different phases were used, along with the spleen tissues of the mice from control group in the same phases. The protein levels of MOF, FOXP3, and H4K16ac were detected through Western blotting. The mRNA expression levels of MOF, TLRS, and FOXP3 were detected by real-time fluorescent quantitative RT-PCR. Co-immunoprecipitation was performed to assess the binding between MOF and FOXP3 in the spleen tissues. ChIP-qPCR was performed to detect the downstream target genes of MOF. The relationships between the protein expression levels of TLRS, FOXP3 in the HCT116 cells, and MOF regulation were also studied. Results The expression levels of MOF and FOXP3 protein in the spleen of EAE mice were significantly higher than those of the control group. The mRNA levels of FOXP3, 山 东 大 学 学 报 (医 学 版)54卷2期 -关景云,等.组蛋白乙酰转移酶MOF在多发性硬化发病机制中的作用 \=-MOF, IL17, TLR4, TLR5, TLR6, TLR7 and TLR9 in EAE mouse spleen tissue were significantly higher than those of the control group(P<0.05); Co-IP showed that MOF directly interacted with FOXP3 in spleen tissues; ChIP-qPCR showed that MOF combined with FOXP3, TLR3, TLR4, TLR5, TLR6, SMAD2, SMAD3, and RoRγt genes in the spleen. TLR4 and FOXP3 showed higher expression levels in the HCT116 cells compared with the control group when MOF was overexpressed(P<0.05). Conclusion MOF suppresses the occurrence of EAE through its interaction with FOXP3.

Key words: Histone acetyltransferase, Treg, Toll-like receptors, MOF, FOXP3