国家自然科学基金重大项目“自身免疫识别与应答的机制及调节研究”结题综述

Final report of major program of National Natural Science Foundation of China“the mechanism and regulation of autoantigen immune recognition and response"

国家自然科学基金重大项目"自身免疫识别与应答的机制及调节研究"围绕自身免疫识别与应答的机制及调节这一免疫学重大基础科学问题,以活化淋巴细胞来源的双链DNA(ALDDNA)免疫小鼠诱导系统性红斑狼疮(SLE)为自身免疫病原型动物模型,研究了DNA的化学修饰及自身免疫识别机制、调节性抗体的产生机制及其在自身免疫应答与调节中的作用、Treg亚群格局的调控及其在自身免疫应答中的作用这3个子科学问题。经过4年研究,以ALD-DNA和活化T细胞膜翻转脂筏相关蛋白为二大自身抗原,在dsDNA免疫原性的化学基础、DNA免疫识别及应答规律、抗T细胞抗体的产生和调节机制、Treg的调控及对自身免疫的调节等方面取得突破性进展,提出基于SAP,Notch1,miR155,Foxo3a,CRT,W8,NK007等的治疗SLE的新策略。

The major program of 'the mechanism and regulation of autoantigen immune recognition and response' is aimed to solve the key basic scientific problem of immunology:the mechanism and regulation of autoantigen immune recognition and response.The program utilizes activated lymphocyte-derived DNA(ALD-DNA)-induced SLE as the major animal model for autoimmune disease.Upon 4-years study on autoimmune diseases induced by ALD-DNA and raft-related proteins translocated onto surface of Tact,breakthrough progress has been achieved in fields including:the chemical basis of immunogenicity of auto-dsDNA,molecular mechanism of autoimmune-recognition and response against ALD-DNA,production and regulatory mechanism of anti-T-cell Abs,regulation of Treg differentiation and its modulation of autoimmune response.These acheivements provide new strategies of treatment for inflammatory autoimmune disease by targeting SAP,Notch1,miR155,Foxo3 a,CRT,W8 and NK007.