Journal of inflammation research · 2026
MAIT Cells Maintain Intestinal Homeostasis Through IL-22 in an Experimental Colitis.
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Peng Yanan, Zheng Chunlan, Wang Youwei, Huang Fengxing, Shao Yu, Liu Lan, Zhao Qiu
Аннотация
OBJECTIVE: Mucosa-associated invariant T (MAIT) cells are a unique subset of innate-like lymphocytes abundant in the gastrointestinal tract, yet their role in maintaining intestinal homeostasis remains incompletely understood. We investigated how MAIT cells contribute to epithelial barrier integrity and the molecular mechanisms underlying this process during experimental colitis.
METHODS: Acute colitis was induced by dextran sulfate sodium (DSS) in wild-type (WT) and MR1-deficient (MR1-/-) mice. Disease severity was quantified via weight loss, colon length, and histopathology. Barrier function was assessed by FITC-dextran permeability and expression of tight junction proteins (ZO-1 and Claudin-1). Single-cell RNA sequencing (scRNA-seq) was employed to identify MAIT-cell- associated mediators, followed by rescue experiments with recombinant IL-22 or CCL2.
RESULTS: MAIT cells accumulated in the inflamed colon and displayed a tissue-specific activated phenotype during DSS-induced colitis. MR1-/- mice developed more severe colitis than WT mice, with aggravated mucosal injury, increased inflammatory cytokine production, disrupted tight junction expression, enhanced intestinal permeability, and increased bacterial translocation. MAIT cell deficiency was associated with markedly reduced colonic IL-22 expression and impaired IL-22 production across multiple immune populations, including Th22 cells, Th17 cells, ILC3s, and CD4⁺ T cells. Recombinant IL-22 partially alleviated colitis and improved barrier-associated protein expression, indicating that IL-22 is an important downstream mediator of MAIT cell-dependent protection. Mechanistically, single-cell RNA sequencing identified CCL2 as a MAIT-associated soluble factor induced during colitis. In vivo CCL2 supplementation restored AHR/CYP1A1 expression, enhanced IL-22 production in Th22 and other lymphocyte subsets, and ameliorated epithelial barrier damage and disease severity in MR1-/- mice.
CONCLUSION: Our study identifies a novel MAIT-CCL2-AHR-IL-22 regulatory axis that that contributes to epithelial barrier protection during acute experimental colitis. MAIT cells appear to act not only as effector cells but also as upstream coordinators of IL-22-dependent mucosal repair, providing a mechanistic basis for targeting this pathway in intestinal inflammatory disease.
METHODS: Acute colitis was induced by dextran sulfate sodium (DSS) in wild-type (WT) and MR1-deficient (MR1-/-) mice. Disease severity was quantified via weight loss, colon length, and histopathology. Barrier function was assessed by FITC-dextran permeability and expression of tight junction proteins (ZO-1 and Claudin-1). Single-cell RNA sequencing (scRNA-seq) was employed to identify MAIT-cell- associated mediators, followed by rescue experiments with recombinant IL-22 or CCL2.
RESULTS: MAIT cells accumulated in the inflamed colon and displayed a tissue-specific activated phenotype during DSS-induced colitis. MR1-/- mice developed more severe colitis than WT mice, with aggravated mucosal injury, increased inflammatory cytokine production, disrupted tight junction expression, enhanced intestinal permeability, and increased bacterial translocation. MAIT cell deficiency was associated with markedly reduced colonic IL-22 expression and impaired IL-22 production across multiple immune populations, including Th22 cells, Th17 cells, ILC3s, and CD4⁺ T cells. Recombinant IL-22 partially alleviated colitis and improved barrier-associated protein expression, indicating that IL-22 is an important downstream mediator of MAIT cell-dependent protection. Mechanistically, single-cell RNA sequencing identified CCL2 as a MAIT-associated soluble factor induced during colitis. In vivo CCL2 supplementation restored AHR/CYP1A1 expression, enhanced IL-22 production in Th22 and other lymphocyte subsets, and ameliorated epithelial barrier damage and disease severity in MR1-/- mice.
CONCLUSION: Our study identifies a novel MAIT-CCL2-AHR-IL-22 regulatory axis that that contributes to epithelial barrier protection during acute experimental colitis. MAIT cells appear to act not only as effector cells but also as upstream coordinators of IL-22-dependent mucosal repair, providing a mechanistic basis for targeting this pathway in intestinal inflammatory disease.