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Background Intestinal fibrosis is a common complication of inflammatory bowel disease, and its core pathogenesis is fibroblast activation and massive extracellular matrix (ECM) deposition. In recent years, innate lymphoid cells (ILCs) have been shown to be an important source of fibroblast activation signals in fibrotic diseases. This study aims to explore the heterogeneity of ILC3 in intestinal fibrosis and the mechanism of its interaction with stromal cells. Methods The intestinal fibrosis model was constructed with ILC3 deficiency mice (Rorc knock-out) treated with chronic DSS/TNBS. Flow cytometry was performed to detect the proportion of ILC3 subsets and cytokine expression level. ILC3 was sorted out for transcriptome sequencing and co-culture experiment with primary intestinal fibroblasts. Results In chronic DSS/TNBS models, the colon CCR6+ILC3 significantly expanded (pin vitro. The expression level of α-SMA protein was significantly upregulated (pCD74 existing in all of them. Flow cytometry confirmed the expression of CD74 on ILC3 for the first time, which is specifically present on CCR6+ILC3 within RORãt+ cells. Cell stimulation experiments in vitro showed that macrophage migration inhibitory factor (MIF)-CD74 signal upregulated IL-22 level in ILC3 cells. Conclusions CCR6+ILC3 is enriched in the intestinal fibrotic microenvironment and can continuously promote disease progression by activating fibroblasts through IL-22. CCR6+ILC3 can sense the pathogenic inflammatory factor MIF in chronic colitis through CD74 and increase IL-22 expression.
Zhao et al. (Thu,) studied this question.