title: CD137 facilitates the resolution of acute DSS-induced colonic inflammation in mice.
abstract: BACKGROUND
  CD137 and its ligand (CD137L) are potent immunoregulatory molecules that influence activation, proliferation, differentiation and cell death of leukocytes. Expression of CD137 is upregulated in the lamina propria cells of Crohn's disease patients. Here, the role of CD137 in acute Dextran-Sodium-Sulfate (DSS)-induced colitis in mice was examined.
  
  
  METHODS
  We induced acute large bowel inflammation (colitis) via DSS administration in CD137(-/-) and wild-type (WT) mice. Colitis severity was evaluated by clinical parameters (weight loss), cytokine secretion in colon segment cultures, and scoring of histological inflammatory parameters. Additionally, populations of lamina propria mononuclear cells (LPMNC) and intraepithelial lymphocytes (IEL) were characterized by flow cytometry. In a subset of mice, resolution of intestinal inflammation was evaluated 3 and 7 days after withdrawal of DSS.
  
  
  RESULTS
  We found that both CD137(-/-) and WT mice demonstrated a similar degree of inflammation after 5 days of DSS exposure. However, the resolution of colonic inflammation was impaired in the absence of CD137. This was accompanied by a higher histological score of inflammation, and increased release of the pro-inflammatory mediators granulocyte macrophage colony-stimulating factor (GM-CSF), CXCL1, IL-17 and IFN-γ. Further, there were significantly more neutrophils among the LPMNC of CD137(-/-) mice, and reduced numbers of macrophages among the IEL.
  
  
  CONCLUSIONS
  We conclude that CD137 plays an essential role in the resolution of acute DSS-induced intestinal inflammation in mice.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Martínez Gómez
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
authors.forename: Thomas
authors.initials: T
authors.lastname: Karrasch
mesh_terms: D000208:Acute Disease; D000818:Animals; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016264:Dextran Sulfate / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000172:deficiency / Q000378:metabolism*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D016264:Dextran Sulfate
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