title: TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis.
abstract: TRAF6 has a key role in the regulation of innate immune responses by mediating signals from both TNF receptor and interleukin-1 receptor/Toll-like receptor superfamilies. Here we show that T cell-specific deletion of TRAF6 unexpectedly results in multiorgan inflammatory disease. TRAF6-deficient T cells exhibit hyperactivation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway compared with wild-type T cells and, as a result, become resistant to suppression by CD4+ CD25+ regulatory T cells. These data identify a previously unrecognized role for TRAF6 in the maintenance of peripheral tolerance, and suggest the presence of a T cell-intrinsic control mechanism to render responder T cells susceptible to tolerizing signals.
authors.affiliation: Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Carolyn G
authors.initials: CG
authors.lastname: King
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Cejas
authors.forename: Taesoo
authors.initials: T
authors.lastname: Kim
authors.forename: Kwiyeom
authors.initials: K
authors.lastname: Yoon
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Kim
authors.forename: Elise
authors.initials: E
authors.lastname: Chiffoleau
authors.forename: Somia P
authors.initials: SP
authors.lastname: Hickman
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Walsh
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D006706:Homeostasis / Q000276:immunology*; D007108:Immune Tolerance / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000502:physiology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D048029:TNF Receptor-Associated Factor 6 / Q000172:deficiency / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D048029:TNF Receptor-Associated Factor 6; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt