ICOS/ICOSL通过调控Tfh/B细胞相互作用和肥大细胞免疫应答参与慢性自发性荨麻疹过敏反应的作用机制及临床意义

慢性自发性荨麻疹（CSU）是皮肤科临床最常见疾病之一，T细胞免疫失衡、自身抗体和肥大细胞（MCs）过度激活均参与了其发病进程，但其确切机制尚未明确。我们前期研究结果显示，共刺激分子ICOS及其配体ICOSL在CSU患者体内表达显著上调，与疾病严重程度等指标显著正相关，因从我们提出以下假说：ICOS/ICOSL信号可能通过调节Tfh细胞的免疫应答，进而促进B细胞的Ig的分泌，并在局部皮损处激活效应肥大细胞，从而参与了CSU患者的自身免疫进程和过敏反应，本项目拟开展以下研究进一步探索ICOS/ICOSL：1）在CSU患者体内的表达及临床意义；2) 信号异常对Tfh细胞亚群和B细胞免疫应答的影响和机制；3）对皮肤肥大细胞功能的影响和具体机制；4）在CSU模型小鼠发病进程中的作用。由此从ICOS/ICOSL/自身免疫/过敏这一全新视角探寻对CSU有临床应用意义新的免疫干预靶点。

Chronic spontaneous urticaria (CSU) is one of the most common clinical allergic diseases in the skin. T cell immune imbalance, autoantibody, and mast cell (MCs) overactivation are involved in the pathogenesis of CSU, but the exact mechanism is not clear. Our preliminary results show that Costimulatory molecular ICOS and their ligand ICOSL expression in CSU patients significantly raised, and positively correlated with the severity of disease index, thus we put forward the following hypothesis: the ICOS/ICOSL signal may regulate T cell immune response, and promote the secretion of the immunoglobulin from B cells, and affect the activation of mast cells locally in skin lesions, then participate in the CSU in patients with the autoimmune process and allergic reaction, this project intends to carry out the following experiments to further explore ICOS/ICOSL: 1) expression in CSU patients and its clinical significance; 2) influence and mechanism of signal abnormality on immune responses of T cell subsets and B cells; 3) the effect on the function of skin mast cells and the specific mechanism; 4) role in the pathogenesis of CSU model mice. Therefore, from the perspective of ICOS/ICOSL/ autoimmunity/allergy, new immune intervention targets with clinical significance for CSU will be explored.