Journal
NATURE IMMUNOLOGY
Volume 16, Issue 2, Pages 188-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3077
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Funding
- US National Institutes of Health [R56AI083304, 01HL018646, R21AI105607, T32AI007529, P01AI56299]
- Cancer Research Institute [1S10RR023440]
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Foxp3(+) regulatory T cells (T-reg cells) are required for immunological homeostasis. One notable distinction between conventional T cells (T-conv cells) and T-reg cells is differences in the activity of phosphatidylinositol-3-OH kinase (PI(3)K); only T-conv cells downregulate PTEN, the main negative regulator of PI(3)K, upon activation. Here we found that control of PI(3)K in T-reg cells was essential for lineage homeostasis and stability. Mice lacking Pten in T-reg cells developed an autoimmune-lymphoproliferative disease characterized by excessive T helper type 1 (T(H)1) responses and B cell activation. Diminished control of PI(3)K activity in T-reg cells led to reduced expression of the interleukin-2 (IL-2) receptor alpha 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 T-reg cells is critical for maintaining their homeostasis, function and stability.
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