title: Heme oxygenase-1 is not required for mouse regulatory T cell development and function.
abstract: CD4 regulatory T cells (Treg) ensure peripheral tolerance to self-antigens and limit the deleterious effects associated with inflammatory and immune responses by mechanisms that remain to be fully understood. The enzyme heme oxygenase-1 (HO-1), through its known anti-inflammatory activity, is a candidate for a functional role in Treg activity. We compared wild-type and heme oxygenase-1-deficient (hmox-1(-/-)) mice in order to assess the role of HO-1 in mouse Treg development and function under physiologic conditions. The frequency of CD25+ and Foxp3+ Treg was similar in hmox-1(-/-) and hmox-1(+/+) mice. More importantly, CD4+ CD25+ Treg purified from either hmox-1(-/-) or hmox-1(+/+) mice were equally efficient in controlling the proliferation in vitro and the expansion in vivo of CD4+ CD25- T cells, whether or not these responder cells expressed HO-1. In addition, induction of expression of HO-1 in vivo did not affect Treg suppressor function. As shown before, expression of HO-1 was higher in Treg than in naive T cells; however, naturally activated Foxp3- T cells displayed equal amount of HO-1 mRNA as Treg. Finally, we conclude that under physiological conditions in mice, Treg development, maintenance and function are independent of HO-1 activity.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, Apartado 14, 2780-901 Oeiras, Portugal.
authors.forename: Santiago
authors.initials: S
authors.lastname: Zelenay
authors.forename: Angelo
authors.initials: A
authors.lastname: Chora
authors.forename: Miguel P
authors.initials: MP
authors.lastname: Soares
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Demengeot
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D051547:Heme Oxygenase-1