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

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is affecting a growing global population. Unlike UC, which is characterized by inflammation confined to the intestinal mucosa and submucosa, CD involves transmural inflammation of the intestine. Although the lymphatic system is believed to play a role in the pathogenesis of CD, its exact contribution remains poorly understood. Mesenteric lymphatics (MLs), which drain interstitial fluid and immune cells into mesenteric lymph nodes, have been implicated in this process. In the present study, we aimed to investigate the role of ML immune cells in TNBS-induced colitis in rats. Flow cytometry analysis revealed an increased ratio of B cells and altered B cell function in the MLs of colitis rats compared to controls. The adoptive transfer of mesenteric lymphatic B (MLB) cells isolated from colitis rats to recipient rats exacerbated colitis and was associated with the enhanced migration of MLB cells to the gut. RNA sequencing analysis demonstrated a significant upregulation of genes associated with inflammation and immune responses in MLB cells from colitis rats, particularly key molecules involved in T cell activation, such as cluster of differentiation 27 (Cd27) and cluster of differentiation 40 (Cd40), and the chemotactic receptor C-C motif chemokine receptor 8 (Ccr8), which mediates B cell migration in response to T cells. Mechanistically, MLB cells from colitis rats were recruited to the colon by intra-intestinal T cells through the Ccr8-C-C motif chemokine ligand 1 (Ccl1) axis, where they subsequently exacerbated inflammatory responses via enhanced differentiation. These observations indicate that the migration of MLB cells to the gut exacerbates TNBS-induced colitis in rats by modulating intestinal T cells.