滤泡性辅助T淋巴细胞在系统性红斑狼疮发病机制中的作用

Role of follicular helper T lymphocytes in the pathogenesis of systemic lupus erythematosus

滤泡性辅助T淋巴细胞是近年发现的一种CD4^＋T细胞亚群，具有独立的细胞表型CD4^＋CD57^＋CXCR5^＋，表达细胞因子（白细胞介素6、21和27）及转录因子（B细胞淋巴瘤6、ICOS和程序性死亡受体1）。滤泡性辅助T淋巴细胞表达的细胞因子不仅作为表面标志，且影响自身的分化及功能，与自身免疫性疾病相关，对B细胞活化和抗体产生具有重要作用，调控滤泡性辅助T淋巴细胞的平衡对促进免疫耐受和阻止自身免疫至关重要。滤泡性辅助T淋巴细胞的调节涉及细胞迁移、分化、成熟等过程，趋化因子受体5是B细胞归巢趋化因子受体，B细胞淋巴瘤6主导了滤泡性辅助T淋巴细胞的分化成熟，ICOS缺失将导致滤泡性辅助T淋巴细胞的过度增长，程序性死亡受体1信号的缺失促进滤泡性辅助T淋巴细胞的产生。研究显示，滤泡性辅助T淋巴细胞可能在参与SLE致病及维持自身免疫病理机制中起作用，无论是SLE患者或鼠SLE模型中滤泡性辅助T淋巴细胞比例均明显增多，并与疾病发展程度、自身抗体水平呈相关性。近期研究表明，SLE患者白细胞介素21水平升高，并与滤泡性辅助T淋巴细胞水平相关。滤泡性辅助T淋巴细胞可能是治疗或阻止SLE病情发展的靶点之一。

Follicular helper T lymphocytes （Tfh cells）, one kind of recently identified CD4＊ T cell subset with independent cell phenotype （CD4＋CD57＊CXCR5＋）, express cytokines including interleukin-6 （IL-6）, IL-21 and IL-27, as well as transcription factors such as B-cell lymphoma 6 （BCL6）, inducible costimulatory molecule （ICOS） and programmed death-1 （PD-1 ）. Cytokines expressed by Tfh cells not only serve as surface markers, but also affect differentiation and function of Tfh cells. Tfh ceils are associated with autoimmune diseases, and play an important role in B cell activation and antibody production, so regulation of Tfh cell balance is crucial for promoting immune tolerance and preventing autoimmunity. The regulation of Tfh cells involves cell migration, differentiation, maturation and other processes. CXC chemokine receptor 5 （CXCRS）is a B-cell-homing chemokine receptor, and BCL6 plays a dominant role in the differentiation and maturation of Tfh cells. ICOS absence leads to excessive growth of Tfh cells, and the absence of PD- 1 signaling promotes the generation of Tfh cells. Studies have shown that Tfh cells may play an important role in the pathogenesis of systemic lupus erythematosus （SLE） and maintenance of autoimmune pathology. In both patients with and mouse models of SLE, the percentage of Tfh cells was significantly increased and correlated with disease progression and autoantibody levels. Recent studies have shown that elevated levels of IL-21 are associated with Tfh cell levels in the patients with SLE. In summary, Tfh cells may be an effective target for the treatment or prevention of SLE disease progression.