title: Burn injury influences the T cell homeostasis in a butyrate-acid sphingomyelinase dependent manner.
abstract: Following burn injury, a key factor for patients susceptible to opportunistic infections is immune suppression. Butyrate levels are important in maintaining a functional immune system and these levels can be altered after injury. The acid sphingomyelinase (Asm) lipid signaling system has been implicated in a T cell actions with some evidence of being influenced by butyrate. Here, we hypothesized that burn-injury changes in butyrate levels would mediate Asm activity and, consequently, T cell homeostasis. We demonstrate that burn injury temporally decreases butyrate levels. We further determined that T cell Asm activity is increased by butyrate and decreased after burn injury. We additionally observed decreased T cell numbers in Asm-deficient, burn-injured, and microbiota-depleted mice. Finally, we demonstrate that butyrate reduced T cell death in an Asm-dependent manner. These data suggest that restoration of butyrate after burn injury may ameliorate the T cell lost observed in burn-injured patients by Asm regulation.
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Rice
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Armocida
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Kuethe
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Emily F
authors.initials: EF
authors.lastname: Midura
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Ayushi
authors.initials: A
authors.lastname: Jain
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hildeman
authors.affiliation: James L. Winkle College of Pharmacy, Division of Pharmacy Practice and Administrative Sciences, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Healy
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA; Department of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, USA. Electronic address: charles.caldwell@uc.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000276:immunology*; D002087:Butyrates / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D002087:Butyrates; D013108:Sphingomyelin Phosphodiesterase
keywords: Acid sphingomyelinase; Apoptosis; Burn injury; Butyrate; T cells