title: Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC), an intestinal inflammatory disease affecting premature infants, is associated with low regulatory T (Treg) to effector T (Teff) cell ratios. We recently demonstrated that heme oxygenase-1 (HO-1) deficiency leads to increased NEC development. Here, we investigated the effects of HO-1 on T-cell proportions in a murine NEC-like injury model.
  
  
  METHODS
  Intestinal injury was induced in 7-d-old wild-type (WT) or HO-1 heterozygous (HO-1 Het) pups by formula-feeding every 4 h for 24-78 h by oral gavage and exposures to 5%O2. Controls remained breastfed. HO-1 was induced in WT pups by administering heme preinjury induction. Lamina propria T cells were identified by flow cytometry. For adoptive transfer studies, WT splenic/thymic Tregs were injected intraperitoneally into HO-1 Het pups 12-24 h preinduction.
  
  
  RESULTS
  Het mice showed increased intestinal injury and decreased Treg/Teff ratios. Genes for pattern recognition (Toll-like receptor-4, C-reactive protein, MyD88) and neutrophil recruitment increased in Het pups after NEC induction. Inducing intestinal HO-1 decreased NEC scores and incidence, and increased Treg/Teff ratios. Moreover, adoptive transfer of Tregs from WT to HO-1 Het pups decreased NEC scores and incidence and restored Treg/Teff ratios.
  
  
  CONCLUSIONS
  HO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer intestinal protection.
authors: 1] Department of Pediatrics, Stanford University School of Medicine, Stanford, California [2] Vlaams Instituut voor Biotechnologie Inflammation Research Center, Gent, Belgium [3] Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors: Stephanie
authors: S
authors: Schulz
authors: Department of Pathology, Stanford University School of Medicine, Stanford, California.
authors: Karen M
authors: KM
authors: Chisholm
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
authors: Hui
authors: H
authors: Zhao
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
authors: Flora
authors: F
authors: Kalish
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California.
authors: Yang
authors: Y
authors: Yang
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
authors: Ronald J
authors: RJ
authors: Wong
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
authors: David K
authors: DK
authors: Stevenson
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000473:pathology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013997:Time Factors
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse