Related Experiment Video
Updated: Mar 26, 2026
Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies
Published on: June 2, 2021
Over-Expression of CD200 Protects Mice from Dextran Sodium Sulfate Induced Colitis
Zhiqi Chen1, Kai Yu1, Fang Zhu1
1Transplant Research Division, The Toronto Hospital, Department of Surgery and Immunology, University Health Network, University of Toronto, Toronto, Canada.
Background And Aim:
CD200:CD200 receptor (CD200R) interactions lead to potent immunosuppression and inhibition of autoimmune inflammation. We investigated the effect of "knockout"of CD200 or CD200R, or over-expression of CD200, on susceptibility to dextran sodium sulfate (DSS)-induced colitis, a mouse model of inflammatory bowel disease (IBD).
Methods:
Acute or chronic colitis was induced by administration of dextran sodium sulfate (DSS) in four groups of age-matched C57BL/6 female mice: (1) CD200-transgenic mice (CD200tg); (2) wild-type (WT) mice; (3) CD200 receptor 1-deficient (CD200R1KO) mice; and (4) CD200-deficient (CD200KO) mice. The extent of colitis was determined using a histological scoring system. Colon tissues were collected for quantitative RT-PCR and Immunohistochemical staining. Supernatants from colonic explant cultures and mononuclear cells isolated from colonic tissue were used for ELISA.
Results:
CD200KO and CD200R1KO mice showed greater sensitivity to acute colitis than WT mice, with accelerated loss of body weight, significantly higher histological scores, more severe infiltration of macrophages, neutrophils and CD3+ cells, and greater expression of macrophage-derived inflammatory cytokines, whose production was inhibited in vitro (in WT/CD200KO mouse cells) by CD200. In contrast, CD200tg mice showed less sensitivity to DSS compared with WT mice, with attenuation of all of the features seen in other groups. In a chronic colitis model, greater infiltration of Foxp3+ regulatory T (Treg) cells was seen in the colon of CD200tg mice compared to WT mice, and anti-CD25 mAb given to these mice attenuated protection.
Conclusions:
The CD200:CD200R axis plays an immunoregulatory role in control of DSS induced colitis in mice.
Insights
The CD200:CD200R pathway regulates immune responses in mouse models of inflammatory bowel disease. Modulating CD200 expression impacts colitis severity, highlighting its therapeutic potential for IBD.
Area of Science:
- Immunology
- Gastroenterology
- Inflammation Research
Background:
- CD200:CD200 receptor (CD200R) interactions are crucial for immune suppression and reducing autoimmune inflammation.
- Dextran sodium sulfate (DSS)-induced colitis is a widely used mouse model for studying inflammatory bowel disease (IBD).
Purpose of the Study:
- To investigate the impact of CD200 or CD200R deficiency, and CD200 overexpression, on susceptibility to DSS-induced colitis.
- To elucidate the immunoregulatory role of the CD200:CD200R axis in experimental colitis.
Main Methods:
- Induction of acute or chronic colitis in CD200-transgenic, wild-type, CD200 receptor 1-deficient, and CD200-deficient mice using DSS.
- Assessment of colitis severity via histological scoring, quantitative RT-PCR, immunohistochemistry, and ELISA.
- Evaluation of inflammatory cytokine production and immune cell infiltration in colon tissues and cells.
Main Results:
- CD200-deficient and CD200R1-deficient mice exhibited increased susceptibility to acute colitis, characterized by weight loss, higher scores, and elevated inflammatory markers.
- CD200 overexpression in transgenic mice conferred resistance to DSS-induced colitis, attenuating disease severity.
- Increased infiltration of regulatory T cells was observed in CD200-overexpressing mice, suggesting a role in immune modulation.
Conclusions:
- The CD200:CD200R axis plays a significant immunoregulatory role in controlling DSS-induced colitis in mice.
- Targeting the CD200:CD200R pathway may offer a therapeutic strategy for managing inflammatory bowel disease.
