Nature Immunology:PI3K 信號通路控制調節性T細胞種群

2015年1月16日訊 /生物谷BIOON/ --Foxp3陽性的調節性體細胞（Treg， regulatory T cells）在維持機體免疫系統功能平衡重具有至關重要的作用。傳統T細胞（Tconv， conventional T cells）和調節性T細胞之間的一項顯著差別就是PI3K信號通路的活性。靜息態的T細胞中PI3K信號通路由負調控因子PTEN抑制，不會被激活，而當Tconv細胞被激活時PTEN的活性會被下調，但是Treg細胞不會。由此研究者們發現控制Treg細胞中的PI3K信號通路對其種群的的體內平衡和穩定性是不可或缺的。

研究者們使用Treg細胞特異性Pten基因敲除的小鼠建立了一種自身免疫性---淋巴增生的疾病模型，而該患病小鼠表現出過量的1型輔助性T細胞（TH1， T helper 1 cell）反應以及B細胞活化。Treg細胞中缺乏對PI3K信號通路的壓制，從而導致白介素-2受體 亞基CD25的低表達，以及Foxp3陽性CD25陰性的細胞群體聚集，最終這些細胞中的Foxp3表達會完全喪失。

總的來說，本文的數據表明通過PTEN來遏制PI3K信號通路在Treg細胞中的活化對於維持Treg細胞種群的體內平衡、免疫功能和穩定性都是非常關鍵的。（生物谷Bioon.com）

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Nature Immunology doi:10.1038/ni.3077

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

Alexandria Huynh, Michel DuPage, Bhavana Priyadharshini, Peter T Sage, Jason Quiros, Christopher M Borges, Natavudh Townamchai, Valerie A Gerriets, Jeffrey C Rathmell, Arlene H Sharpe, Jeffrey A Bluestone & Laurence A Turka

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.