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PTEN is required for human Treg suppression of costimulation in vitro.
Lam, Avery J; Haque, Manjurul; Ward-Hartstonge, Kirsten A; Uday, Prakruti; Wardell, Christine M; Gillies, Jana K; Speck, Madeleine; Mojibian, Majid; Klein Geltink, Ramon I; Levings, Megan K.
Afiliación
  • Lam AJ; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Haque M; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
  • Ward-Hartstonge KA; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Uday P; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
  • Wardell CM; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Gillies JK; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
  • Speck M; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Mojibian M; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
  • Klein Geltink RI; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Levings MK; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
Eur J Immunol ; 52(9): 1482-1497, 2022 09.
Article en En | MEDLINE | ID: mdl-35746855
Regulatory T-cell (Treg) therapy is under clinical investigation for the treatment of transplant rejection, autoimmune disease, and graft-versus-host disease. With the advent of genome editing, attention has turned to reinforcing Treg function for therapeutic benefit. A hallmark of Tregs is dampened activation of PI3K-AKT signaling, of which PTEN is a major negative regulator. Loss-of-function studies of PTEN, however, have not conclusively shown a requirement for PTEN in upholding Treg function and stability. Using CRISPR-based genome editing in human Tregs, we show that PTEN ablation does not cause a global defect in Treg function and stability; rather, it selectively blocks their ability to suppress antigen-presenting cells. PTEN-KO Tregs exhibit elevated glycolytic activity, upregulate FOXP3, maintain a Treg phenotype, and have no discernible defects in lineage stability. Functionally, PTEN is dispensable for human Treg-mediated inhibition of T-cell activity in vitro and in vivo but is required for suppression of costimulatory molecule expression by antigen-presenting cells. These data are the first to define a role for a signaling pathway in controlling a subset of human Treg activity. Moreover, they point to the functional necessity of PTEN-regulated PI3K-AKT activity for optimal human Treg function.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Linfocitos T Reguladores / Fosfohidrolasa PTEN Límite: Humans Idioma: En Revista: Eur J Immunol Año: 2022 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Linfocitos T Reguladores / Fosfohidrolasa PTEN Límite: Humans Idioma: En Revista: Eur J Immunol Año: 2022 Tipo del documento: Article País de afiliación: Canadá