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Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

(2015) PEDIATRIC RESEARCH. 77(5). p.640-648
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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 wildtype (WT) or HO-1 heterozygous (HO-1 Het) pups by formula-feeding every 4h for 24-78h by oral gavage and exposures to 5%O-2. 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. Conclusion: HO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer intestinal protection.
Keywords
DENDRITIC CELLS, EXPRESSION, IMMUNE-RESPONSES, RAT MODEL, NECROTIZING ENTEROCOLITIS, MICE, INJURY, INTERLEUKIN-10, APOPTOSIS, PROMOTER

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MLA
Kourula, Stephanie et al. “Heme Oxygenase-1 Confers Protection and Alters T-cell Populations in a Mouse Model of Neonatal Intestinal Inflammation.” PEDIATRIC RESEARCH 77.5 (2015): 640–648. Print.
APA
Kourula, S., Chisholm, K. M., Zhao, H., Kalish, F., Yang, Y., Wong, R. J., & Stevenson, D. K. (2015). Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation. PEDIATRIC RESEARCH, 77(5), 640–648.
Chicago author-date
Kourula, Stephanie, Karen M Chisholm, Hui Zhao, Flora Kalish, Yang Yang, Ronald J Wong, and David K Stevenson. 2015. “Heme Oxygenase-1 Confers Protection and Alters T-cell Populations in a Mouse Model of Neonatal Intestinal Inflammation.” Pediatric Research 77 (5): 640–648.
Chicago author-date (all authors)
Kourula, Stephanie, Karen M Chisholm, Hui Zhao, Flora Kalish, Yang Yang, Ronald J Wong, and David K Stevenson. 2015. “Heme Oxygenase-1 Confers Protection and Alters T-cell Populations in a Mouse Model of Neonatal Intestinal Inflammation.” Pediatric Research 77 (5): 640–648.
Vancouver
1.
Kourula S, Chisholm KM, Zhao H, Kalish F, Yang Y, Wong RJ, et al. Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation. PEDIATRIC RESEARCH. 2015;77(5):640–8.
IEEE
[1]
S. Kourula et al., “Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation,” PEDIATRIC RESEARCH, vol. 77, no. 5, pp. 640–648, 2015.
@article{7176309,
  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 wildtype (WT) or HO-1 heterozygous (HO-1 Het) pups by formula-feeding every 4h for 24-78h by oral gavage and exposures to 5%O-2. 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. 
Conclusion: HO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer intestinal protection.},
  author       = {Kourula, Stephanie and Chisholm, Karen M and Zhao, Hui and Kalish, Flora and Yang, Yang and Wong, Ronald J and Stevenson, David K},
  issn         = {0031-3998},
  journal      = {PEDIATRIC RESEARCH},
  keywords     = {DENDRITIC CELLS,EXPRESSION,IMMUNE-RESPONSES,RAT MODEL,NECROTIZING ENTEROCOLITIS,MICE,INJURY,INTERLEUKIN-10,APOPTOSIS,PROMOTER},
  language     = {eng},
  number       = {5},
  pages        = {640--648},
  title        = {Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation},
  url          = {http://dx.doi.org/10.1038/pr.2015.22},
  volume       = {77},
  year         = {2015},
}

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