Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Huynh, A; DuPage, M; Priyadharshini, B; Sage, PT; Quiros, J; Borges, CM; Townamchai, N; Gerriets, VA; Rathmell, JC; Sharpe, AH; Bluestone, JA; Turka, LA

Published Date

  • February 2015

Published In

Volume / Issue

  • 16 / 2

Start / End Page

  • 188 - 196

PubMed ID

  • 25559257

Pubmed Central ID

  • 25559257

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni.3077

Language

  • eng