title: MTG16 contributes to colonic epithelial integrity in experimental colitis.
abstract: OBJECTIVE
  The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8(-/-) and Mtgr1(-/-) mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity.
  
  
  METHODS
  Baseline and stress induced colonic phenotypes were examined in Mtg16(-/-) mice. To unmask phenotypes, we treated Mtg16(-/-) mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation.
  
  
  RESULTS
  Mtg16(-/-) mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16(-/-) mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1(+), F4/80(+), CD11c(+) and MHCII(+); CD11c(+)) and Th1 adaptive (CD4) immune cells in Mtg16(-/-) colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16(-/-) colons. Compared with wild-type mice, Mtg16(-/-) mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wild-type marrow into Mtg16(-/-) recipients did not rescue the Mtg16(-/-) injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16(-/-) mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16(-/-) mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues.
  
  
  CONCLUSIONS
  These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury.
authors: Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee, USA.
authors: Christopher S
authors: CS
authors: Williams
authors: Amber M
authors: AM
authors: Bradley
authors: Rupesh
authors: R
authors: Chaturvedi
authors: Kshipra
authors: K
authors: Singh
authors: Maria B
authors: MB
authors: Piazuelo
authors: Xi
authors: X
authors: Chen
authors: Elizabeth M
authors: EM
authors: McDonough
authors: David A
authors: DA
authors: Schwartz
authors: Caroline T
authors: CT
authors: Brown
authors: Margaret M
authors: MM
authors: Allaman
authors: Lori A
authors: LA
authors: Coburn
authors: Sara N
authors: SN
authors: Horst
authors: Dawn B
authors: DB
authors: Beaulieu
authors: Yash A
authors: YA
authors: Choksi
authors: Mary Kay
authors: MK
authors: Washington
authors: Amanda D
authors: AD
authors: Williams
authors: Melissa A
authors: MA
authors: Fisher
authors: Sandra S
authors: SS
authors: Zinkel
authors: Richard M
authors: RM
authors: Peek
authors: Keith T
authors: KT
authors: Wilson
authors: Scott W
authors: SW
authors: Hiebert
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D016025:Bone Transplantation; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D003093:Colitis, Ulcerative / Q000378:metabolism; D003106:Colon / Q000276:immunology; D016264:Dextran Sulfate; D020895:Enterocytes / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010539:Permeability; D012097:Repressor Proteins; D018417:Th1 Cells / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C117411:Cbfa2t3 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016264:Dextran Sulfate