Derp2表位疫苗通过上调CD22表达促进调节性B细胞分化抑制呼吸道过敏的作用和机理研究

呼吸道过敏性疾病特异性免疫疗法（AIT）的疗效有待提高，其治疗机制仍未完全明了，过敏原B细胞表位疫苗已成为AIT治疗研究新的发展策略。前期我们构建了尘螨过敏原Derp2的B细胞表位疫苗（rDerp2-B），可降低IgE水平、减少T细胞增殖，显示了抑制过敏性炎症的潜力。调节性B细胞（Breg）在AIT治疗中发挥重要免疫调控作用，但其诱导产生机制有待研究。CD22可抑制B细胞活化，且与Breg产生有关。前期研究表明，rDerp2-B疫苗可促进CD22表达，CD22下游信号分子BCL2L12参与了B细胞耐受形成，其表达与CD22呈负相关。我们推测：rDerp2-B可抑制呼吸道过敏炎症，通过上调B细胞CD22表达抑制BCL2L12基因转录，从而诱导Breg产生。本研究将探讨rDerp2-B抑制小鼠呼吸道过敏性炎症效果，并阐明其诱导Breg产生的分子机制。为过敏性疾病AIT治疗策略研究提供理论基础。

The efficacy and safety of allergen-specific immunotherapy (AIT) for respiratory allergic diseases need to be improved, and the mechanism of AIT remains unknown. Allergen B cell epitope vaccine has been becoming a promising strategy for allergic diseases. In the preliminary studies, we have constructed a B-cell epitope peptide fusion vaccine (rDerp2-B) of Derp2, which significantly reduced the serum IgE reactivity, inhibited CD4+T cell proliferation and increased CD22 expression on peripheral B cells from patients with allergic rhinitis. Regulatory B cells (Breg) play an important role in immune regulation during AIT therapy, while its induction mechanism remains to be further explored. CD22 negatively regulates BCR-mediated activation of B cells, which may be related to IL-10+Breg production in AIT therapy. Our studies showed that rDerp2-B vaccine could facilitate CD22 expression, which negatively correlated with its downstream signaling molecule BCL2L12 expression in B cells. We hypothesize that rDerp2-B vaccine can inhibit nasal allergic inflammation in mouse with allergic rhinitis and promote Breg proliferation through suppressing the BCL2L12 transcription by upregulation of CD22 expression on B cells. The proposed study will further evaluate the inhibitive effect of rDerp2-B vaccine on respiratory allergic inflammation, and explore the molecular mechanism of Breg generation during AIT treatment. The expected results will provide a theoretical basis for the development of novel B cell epitope vaccines.