Wnt and Treg-Associated Signaling Coordinate Mucosal Regeneration and MALT Formation in a Mouse Model of Chronic Colitis.

Chronic ulcerative colitis disrupts mucosal-acquired immunity; however, the relationship between mucosal regeneration and mucosa-associated lymph tissue (MALT) development remains unclear. We explored crypt responses, MALT phenotypes, and regulatory T cells (Tregs) in a mouse model of chronic colitis following two cycles of dextran sodium sulfate (DSS) exposure. The mucosal regeneration score correlated with crypt expression of Ki-67 and LGR5, submucosal FOXP3-positive Treg expression, and MALT scores. MALT can be categorized into solitary-isolated lymphoid structures, tertiary lymphoid structures, and colonic patches. Regenerative crypts adjacent to tertiary lymphoid structures exhibit reduced expression of Ki-67, LGR5, and SOX9, which might favor mucosal differentiation. These findings were further supported by correlations between crypt stem cell- and Treg-related colonic gene expression of Lgr5, Sox9, Wnt6, Ccl20, and IL10, and between Tgfb1 and Cxcl13. These results suggested that chronic colitis is repaired by stem cell-mediated mucosal regeneration and differentiation, potentially driven by the development of MALT-containing Tregs.