title: Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice.
abstract: OBJECTIVE
  Imbalance between pro- and anti-inflammatory cytokines produced by intestinal T cells induces inflammatory bowel diseases (IBD). However, the importance of regulation of cytokine signalling in IBD has not been fully clarified. We have demonstrated that suppressor of cytokine signalling 1 (SOCS1) is expressed in inflamed tissues in an experimental colitis model. In the present study, we investigated the role of SOCS1 in colitis models to clarify the mechanism of IBD development.
  
  
  METHODS
  Intestinal T cells in transgenic mice expressing high levels of SOCS1 in lymphocytes (SOCS1Tg mice) were characterised by flow cytometric analysis and cytokine production from intestinal T cells was determined by ELISA. 2,4,6-Trinitrobenzene sulphonic acid (TNBS) induced colitis was induced in SOCS1Tg mice and severity was compared with control littermates by measurement of survival rates. Intracellular signalling was assessed by western blotting analysis.
  
  
  RESULTS
  SOCS1Tg mice developed colitis spontaneously with age. Young SOCS1Tg mice less than 15 weeks of age, before the onset of colitis, were susceptible to TNBS induced colitis. Intestinal T cells of SOCS1Tg mice showed increased interferon gamma and tumour necrosis factor alpha production and decreased transforming growth factor beta production. Expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a negative regulator of T cell activation, in SOCS1Tg mice was severely impaired at the protein level although mRNA levels of CTLA-4 in SOCS1Tg mice were comparable with those in control mice.
  
  
  CONCLUSIONS
  Our data suggest that SOCS1 plays an important role in the regulation of colitis by controlling intestinal T cell activation mediated through CTLA-4 expression.
authors.affiliation: Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. INAGAKI@med.miyazaki-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Inagaki-Ohara
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.forename: G
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Hotokezaka
authors.forename: K
authors.initials: K
authors.lastname: Chijiiwa
authors.forename: M
authors.initials: M
authors.lastname: Kubo
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Nawa
authors.forename: A
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D060908:CTLA-4 Antigen; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D002352:Carrier Proteins; C556707:Ctla4 protein, mouse; D016207:Cytokines; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins