title: An integral role for heme oxygenase-1 and carbon monoxide in maintaining peripheral tolerance by CD4+CD25+ regulatory T cells.
abstract: Over the past decade, a great deal of interest and attention has been directed toward a population of regulatory T cells (Treg) coexpressing the markers CD4 and CD25. The hallmark phenotype of this cell population resides in its ability to dominantly maintain peripheral tolerance and avert autoimmunity. Despite robust research interest in Treg, their mechanism of action and interaction with other cell populations providing immune regulation remains unclear. In this study, we present a model for Treg activity that implicates carbon monoxide, a by-product of heme oxygenase-1 activity, as an important and underappreciated facet in the suppressive capacity of Treg. Our hypothesis is based on recent evidence supporting a role for heme oxygenase-1 in regulating immune reactivity and posit carbon monoxide to function as a suppressive molecule. Potential roles for indoleamine 2,3-dioxygenase, costimulatory molecules, and cytokines in tolerance induction are also presented. This model, if validated, could act as a catalyst for new investigations into Treg function and ultimately result in novel methods to modulate Treg biology toward therapeutic applications.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Brusko
authors.forename: Clive H
authors.initials: CH
authors.lastname: Wasserfall
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Kapturczak
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology*; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D007108:Immune Tolerance; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D015375:Receptors, Interleukin-2; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1