肠系膜淋巴管B细胞在克罗恩病中的作用及机制研究

Crohn’s disease (CD) is characterized by intestinal ulcer close to the mesentery, accompanied by structural abnormalities of mesenteric lymphatics and increased infiltration of mesenteric lymphatic B cells, while there is little research focusing on the pathogenic role of mesenteric lymphatic B cells in CD. Mesenteric lymphatics drainage intestinal lymph and converge to mesenteric lymph nodes (MLN). Our previous study found that B cells in the lamina propria and MLN increased in colitis, and the proportion of B cells increases further when colitis aggravates. Meantime, lymphatic stenosis in CD promotes mesenteric adipose tissue hyperplasia and inflammation. We found that mesenteric adipose tissue B cells could promote local inflammation, and inflamed mesenteric adipose tissue participated in intestinal barrier. These results suggest that mesenteric lymphatic B cells may play an important role in colitis. This study will detect the change of mesenteric lymphatics structure and immune cells in the intestinal segment, and confirm the effects of mesenteric lymphatic B cells on colitis and mesenteric adipose tissue by adoptive transfer, as well as whether B cells can migrate to MLN or intestinal lamina propria. Then, we will explore the interaction between B cells and T cells to clarify the mechanism of mesenteric lymphatic B cells participating in colitis. This study will reveal the relationship between mesenteric lymphatics and colitis, and provide a new direction for clarifying the pathogenesis of CD.

克罗恩病（CD）患者的肠道溃疡多靠近肠系膜侧，同时存在肠系膜淋巴管的结构与功能异常，以及肠系膜淋巴管内B细胞浸润增多，但对于肠系膜淋巴管B细胞对CD的作用及机制鲜有研究报道。肠系膜淋巴管引流肠道淋巴汇入肠系膜淋巴结，申请人前期发现肠炎时肠道固有层和肠系膜淋巴结内B细胞增多，在肠炎加重时B细胞比例进一步升高。CD时淋巴管狭窄可促进肠系膜脂肪增生及炎症，我们发现肠系膜脂肪组织B细胞可促进局部脂肪炎症。这些研究提示肠系膜淋巴管B细胞可能在肠炎中发挥重要作用。本研究将以肠炎时肠系膜淋巴管结构及淋巴管内B细胞变化入手；通过回输实验验证肠系膜淋巴管B细胞对肠炎以及肠系膜脂肪组织的作用，以及其是否可迁移到肠系膜淋巴结和肠道固有层发挥效应；最后从B细胞与T细胞相互作用角度深入探究淋巴管B细胞参与肠炎的可能机制。该研究将进一步揭示肠系膜淋巴管与肠炎的密切关联，为阐明CD的发病机制提供新的方向。

克罗恩病（CD）患者的肠道溃疡多靠近肠系膜侧，同时存在肠系膜淋巴管的结构与功能异常，以及肠系膜淋巴管内B细胞浸润增多，但对于肠系膜淋巴管B细胞对CD的作用及机制鲜有研究报道。.本研究发现TNBS大鼠（CD模型）肠系膜淋巴管内存在淋巴管结构及免疫细胞比例变化；相比于对照组肠系膜淋巴管B细胞，回输TNBS大鼠肠系膜淋巴管B细胞到对应肠炎大鼠后，受体大鼠肠炎更重，明确了肠系膜B细胞加重肠炎的作用；相比于接受对照组B细胞的肠炎大鼠，接受TNBS组淋巴管B细胞的肠炎大鼠，回输入体内的B细胞更快、更多的分布到肠道组织中，以及进入肝脏代谢更快；回输B细胞后，伴随肠炎加重存在T细胞亚型变化；同时体外T-B细胞共培养实验，发现B细胞可调节T细胞分化、炎症因子分泌等作用。.通过以上研究结果，我们认为IBD时不仅存在肠系膜淋巴管的结构及功能变化，且肠系膜淋巴管内免疫细胞，至少B细胞，可通过趋化到肠道、调节肠道T细胞等作用参与IBD的发生发展。从免疫角度研究炎症性肠病这一带有浓厚免疫色彩的炎症疾病具有坚实的理论基础，可为IBD的免疫诊断和免疫治疗等带来广泛的应用前景。