Mesenteric Lymphatic B Cells Migrate to the Gut and Aggravate TNBS-Induced Rat Colitis via Regulating Intestinal T...

Area of Science:

• Gastroenterology
• Immunology
• Lymphatic System Research

Background:

• Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a growing global health concern.
• While the lymphatic system's role in CD pathogenesis is suspected, its precise mechanisms remain unclear.
• Mesenteric lymphatics (MLs) are crucial for draining intestinal fluid and immune cells, but their specific contribution to IBD is under investigation.

Purpose of the Study:

• To investigate the role of immune cells within mesenteric lymphatics (MLs) in the context of TNBS-induced colitis in rats.
• To elucidate the functional and molecular characteristics of mesenteric lymphatic B (MLB) cells during colitis.

Main Methods:

• Flow cytometry was used to analyze immune cell populations and function in MLs of rats with TNBS-induced colitis.
• Adoptive transfer experiments were performed using MLB cells from colitis rats to assess their impact on recipient rats.
• RNA sequencing was employed to identify gene expression changes in MLB cells from colitis rats.

Main Results:

• Colitis rats exhibited an increased ratio of B cells and altered B cell function in MLs.
• Adoptive transfer of MLB cells from colitis rats exacerbated colitis severity and promoted their migration to the gut.
• RNA sequencing revealed upregulation of genes related to T cell activation (Cd27, Cd40) and B cell migration (Ccr8) in MLB cells from colitis rats.

Conclusions:

• Mesenteric lymphatic B cells migrate to the inflamed colon, driven by intra-intestinal T cells via the Ccr8-Ccl1 axis.
• These migrating MLB cells exacerbate colitis by enhancing inflammatory responses through differentiation.
• Targeting MLB cell migration or function presents a potential therapeutic strategy for inflammatory bowel disease.