Free radical biology & medicine · 2026
CD200R protects against ulcerative colitis by regulating macrophage polarization and intestinal barrier function: evidence from human patients and mouse disease models.
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Liu Xiaoming, Hu Yang, Wang Jin, Ruan Qing, Chen Yujie, Guo Xiaoya, Peng Lei, Ke Xiquan, Guo Zhiguo
Аннотация
BACKGROUND AND OBJECTIVE: Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by dysregulated mucosal immunity and impaired epithelial barrier function. CD200R is an inhibitory immune receptor involved in immune homeostasis, but its cell-specific expression pattern and functional role in UC remain unclear.
METHODS: We reanalyzed single-cell RNA sequencing (scRNA-seq) data from human UC colonic tissues to characterize CD200R expression at cellular resolution. CD200R expression was further validated in colonic biopsies from UC patients and non-IBD controls. Functional roles of CD200R were investigated using DSS-induced colitis models in global CD200R-deficient mice and AAV-mediated CD200R-overexpressing mice. In vitro RAW264.7 macrophage experiments and Caco-2 epithelial assays were performed to assess macrophage polarization, oxidative stress, epithelial barrier integrity, and downstream signaling pathways.
RESULTS: scRNA-seq analysis revealed that CD200R expression was predominantly reduced in intestinal macrophages in UC, accompanied by activation of inflammatory signaling pathways. Consistently, CD200R expression was decreased in UC patient tissues and correlated with disease severity. In vivo, CD200R deficiency aggravated DSS-induced colitis, enhanced oxidative stress, promoted M1 macrophage polarization, and disrupted epithelial barrier integrity. In contrast, CD200R overexpression alleviated intestinal inflammation, promoted M2 polarization, and preserved barrier function. Transcriptomic and protein analyses further identified changes in AMPK/PPARγ and TLR4/NF-κB-related signaling associated with CD200R modulation.
CONCLUSIONS: Reduced CD200R expression is associated with intestinal inflammation in UC. Integrated analyses of human tissues, single-cell transcriptomic data, and experimental models suggest that CD200R may contribute to the regulation of macrophage polarization, oxidative stress, and epithelial barrier function, supporting further investigation of CD200R as a candidate therapeutic axis in UC.
METHODS: We reanalyzed single-cell RNA sequencing (scRNA-seq) data from human UC colonic tissues to characterize CD200R expression at cellular resolution. CD200R expression was further validated in colonic biopsies from UC patients and non-IBD controls. Functional roles of CD200R were investigated using DSS-induced colitis models in global CD200R-deficient mice and AAV-mediated CD200R-overexpressing mice. In vitro RAW264.7 macrophage experiments and Caco-2 epithelial assays were performed to assess macrophage polarization, oxidative stress, epithelial barrier integrity, and downstream signaling pathways.
RESULTS: scRNA-seq analysis revealed that CD200R expression was predominantly reduced in intestinal macrophages in UC, accompanied by activation of inflammatory signaling pathways. Consistently, CD200R expression was decreased in UC patient tissues and correlated with disease severity. In vivo, CD200R deficiency aggravated DSS-induced colitis, enhanced oxidative stress, promoted M1 macrophage polarization, and disrupted epithelial barrier integrity. In contrast, CD200R overexpression alleviated intestinal inflammation, promoted M2 polarization, and preserved barrier function. Transcriptomic and protein analyses further identified changes in AMPK/PPARγ and TLR4/NF-κB-related signaling associated with CD200R modulation.
CONCLUSIONS: Reduced CD200R expression is associated with intestinal inflammation in UC. Integrated analyses of human tissues, single-cell transcriptomic data, and experimental models suggest that CD200R may contribute to the regulation of macrophage polarization, oxidative stress, and epithelial barrier function, supporting further investigation of CD200R as a candidate therapeutic axis in UC.