title: Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability.
abstract: Foxp3(+) regulatory T cells (Treg cells) are required for immunological homeostasis. One notable distinction between conventional T cells (Tconv cells) and Treg cells is differences in the activity of phosphatidylinositol-3-OH kinase (PI(3)K); only Tconv cells downregulate PTEN, the main negative regulator of PI(3)K, upon activation. Here we found that control of PI(3)K in Treg cells was essential for lineage homeostasis and stability. Mice lacking Pten in Treg cells developed an autoimmune-lymphoproliferative disease characterized by excessive T helper type 1 (TH1) responses and B cell activation. Diminished control of PI(3)K activity in Treg cells led to reduced expression of the interleukin-2 (IL-2) receptor α subunit CD25, accumulation of Foxp3(+)CD25(-) cells and, ultimately, loss of expression of the transcription factor Foxp3 in these cells. Collectively, our data demonstrate that control of PI(3)K signaling by PTEN in Treg cells is critical for maintaining their homeostasis, function and stability.
authors.affiliation: 1] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. [2] Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Alexandria
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Diabetes Center and the Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: DuPage
authors.affiliation: Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Priyadharshini
authors.affiliation: Division of Immunology, Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Sage
authors.affiliation: Diabetes Center and the Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Quiros
authors.affiliation: 1] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. [2] Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Borges
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: Natavudh
authors.initials: N
authors.lastname: Townamchai
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Gerriets
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Rathmell
authors.affiliation: Division of Immunology, Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.affiliation: Diabetes Center and the Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.affiliation: 1] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. [2] Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017353:Gene Deletion; D006706:Homeostasis / Q000276:immunology*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase