title: Establishment of a novel mouse model of ulcerative colitis with concomitant cytomegalovirus infection: in vivo identification of cytomegalovirus persistent infected cells.
abstract: BACKGROUND
  Human cytomegalovirus (HCMV) infection is considered to be an exacerbating factor in patients with ulcerative colitis (UC). However, the pathogenicity of HCMV in the exacerbation of UC remains unclear. The lack of a model mimicking UC with HCMV infection has posed a challenge for research into the pathogenic mechanism of HCMV in flare of UC. Therefore, the aim of our study was to establish a new mouse model of UC with HCMV infection.
  
  
  METHODS
  We established latent murine CMV (MCMV) infection in T-cell receptor α knockout (TCR-α KO) mice at an early age by adjustment of viral dose. Next, we performed immunohistochemical analysis in various organs of infected adult TCR-α KO mice to prove the correlation between MCMV infection and development of colitis. We then assessed colitis histologically and cytokine expression in the colon of infected and uninfected TCR-α KO mice. Finally, the types of MCMV-infected cells in the inflamed colon were examined by immunohistochemical analysis.
  
  
  RESULTS
  MCMV antigen-positive cells reappeared predominantly in the inflamed colon of TCR-α KO mice. Severe colitis developed in the infected TCR-α KO mice compared with uninfected mice, and Th1/Th17 and Th2 responses were strongly induced. MCMV-infected cells were mainly perivascular stromal cells including pericytes, expressing platelet-derived growth factor receptor-beta (PDGFR-β) and CXC chemokine ligand 12 (CXCL12).
  
  
  CONCLUSIONS
  In this study, we established, to our knowledge, the first mouse model of UC with HCMV infection. This model is an excellent tool for clarifying the detailed pathogenicity of HCMV in the exacerbation of UC and developing new treatment strategy for active UC with HCMV infection.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Matsumura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Isao
authors.initials: I
authors.lastname: Kosugi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Honzawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Yoshino
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsuura
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Arai
authors.forename: Toshihide
authors.initials: T
authors.lastname: Iwashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta