title: Over-Expression of CD200 Protects Mice from Dextran Sodium Sulfate Induced Colitis.
abstract: OBJECTIVE
  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.
authors: Transplant Research Division, The Toronto Hospital, Department of Surgery and Immunology, University Health Network, University of Toronto, Toronto, Canada.
authors: Zhiqi
authors: Z
authors: Chen
authors: Transplant Research Division, The Toronto Hospital, Department of Surgery and Immunology, University Health Network, University of Toronto, Toronto, Canada.
authors: Kai
authors: K
authors: Yu
authors: Transplant Research Division, The Toronto Hospital, Department of Surgery and Immunology, University Health Network, University of Toronto, Toronto, Canada.
authors: Fang
authors: F
authors: Zhu
authors: Transplant Research Division, The Toronto Hospital, Department of Surgery and Immunology, University Health Network, University of Toronto, Toronto, Canada.
authors: Reginald
authors: R
authors: Gorczynski
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D015703:Antigens, CD; C492346:CD200 receptor, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; D016264:Dextran Sulfate; D004318:Doxycycline; C042739:antigens, CD200