Department of Laboratory Medicine, West China Second University Hospital, and Key Laboratory of Obstetric and Gynecolohic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, China.
State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China.
Front Immunol. 2022 Sep 12;13:997862. doi: 10.3389/fimmu.2022.997862. eCollection 2022.
CXCL13 is a chemokine that is widely involved in the pathogenesis of autoimmune diseases, tumors and inflammatory diseases. In this study, we investigate the role of CXCL13 in the pathogenesis of inflammatory bowel disease using both clinical specimens and animal models. We found that the serum CXCL13 concentration in IBD patients was significantly higher than that in healthy controls, and correlated with that of CRP, neutrophils counts and hemoglobin. The increase of CXCL13 in IBD patients might be related to the significant decrease of circulating CD4+CXCR5+ T cells, the increase of CD19+CD5+ B cells and the enhancement of humoral immunity. In mice colitis model, we also found elevated levels of CXCL13 in colon tissue. knockout mice exhibited a mild, self-limiting form of disease. Additionally, CXCL13 deficiency restricted CD4+CXCR5+ T cells migration in mesenteric lymph nodes, resulting locally regulatory B cells increased in colon. In conclusion, our findings raise the possibility that CXCL13 plays a critical role in the pathogenesis of IBD. We believe that our findings will contribute to the understanding of the etiology, and that antagonizing or inhibiting CXCL13 may work as a potential adjunctive therapy strategy for patients with IBD.
趋化因子(C-X-C 基元)配体 13(CXCL13)广泛参与自身免疫性疾病、肿瘤和炎症性疾病的发病机制。在这项研究中,我们使用临床标本和动物模型来研究 CXCL13 在炎症性肠病发病机制中的作用。我们发现,IBD 患者的血清 CXCL13 浓度明显高于健康对照者,且与 CRP、中性粒细胞计数和血红蛋白相关。IBD 患者中 CXCL13 的增加可能与循环 CD4+CXCR5+T 细胞的显著减少、CD19+CD5+B 细胞的增加和体液免疫的增强有关。在小鼠结肠炎模型中,我们还发现结肠组织中 CXCL13 水平升高。CXCL13 基因敲除小鼠表现出轻度、自限性疾病。此外,CXCL13 缺乏限制了肠系膜淋巴结中 CD4+CXCR5+T 细胞的迁移,导致结肠中局部调节性 B 细胞增加。总之,我们的研究结果表明,CXCL13 在 IBD 的发病机制中起关键作用。我们相信,我们的研究结果将有助于了解病因,拮抗或抑制 CXCL13 可能成为 IBD 患者的一种潜在辅助治疗策略。