潘多拉魔盒的秘密：兼职蛋白特异性IgE的产生机制及其在免疫性疾病中的潜在意义

免疫耐受对维持机体内环境稳定至关重要，但其机制尚未完全明了。课题组首次发现，IL-33可改变机体对自身抗原、弱抗原或外源性抗原的不应答或低应答状态，诱导特异性IgE产生并加重炎症损伤，该抗体可特异性识别细菌性兼职蛋白。故提出“体内外多种因素刺激机体促使IL-33表达增高，从而打破机体免疫耐受诱导产生特异性IgE，后者可能通过识别动/植物、微生物与机体正常组织细胞间相同或相似的兼职蛋白抗原表位，以‘分子模拟’方式引起机体针对相应‘交叉抗原’的应答导致免疫病理损伤”。为证实上述理论，本课题拟采用多种技术手段研究IL-33打破免疫耐受诱导机体产生兼职蛋白特异性IgE和该抗体通过交叉识别造成免疫损伤的机制，探讨兼职蛋白共同/优势表位肽在临床应用中的意义，为有效控制IgE引起的相关疾病奠定基础。本课题是源头创新工作，深入探索有望为阐释免疫耐受机制和某些临床疾病现象提供新的理论和实验依据。

Immune tolerance is essential to maintain the normal physiological state of the body, which is closely associated with the occurrence and development of many diseases. Our group found that IL-33 can alter the status of the host’s non- or low-response to autoantigen, weak antigen or even exogenous antigen, and induces production of specific IgE and aggravates inflammatory damage. Such specific IgE can recognize bacterial moonlighting proteins. In our knowledge, this finding is the first time in the world. Based on these data, we raised a novel theory, that is, many factors are able to increase the expression of IL-33 which breaks down the body's immune tolerance and induces production of specific IgE. Such IgE antibody might recognize the same or similar the epitopes of moonlighting proteins of animals, plants, microorganisms, normal tissues and cells. Such recognition causes the body to respond to the corresponding “cross-antigen” and results in immune-mediated pathological damage through a manner of “molecular mimicry”. To verify the above theory, using various technological means we aimed to 1) reveal the mechanism by which IL-33 breaks down immune tolerance and induce production of specific IgE in the body; 2) elucidate the mechanism by which specific IgE antibody against moonlighting proteins causes immune damage through cross-recognition, and 3) explore the clinical significance of the common/predominant epitope peptides of moonlighting protein, which will lay the foundation for effective control of related diseases caused by IgE. This study is also the source of original innovation. Further deeply exploration of our findings is expected to provide new theoretical and experimental evidence for the interpretation of the mechanisms of immune tolerance and some clinical disease phenomena.