表達(dá)Foxp3的“調(diào)控性T細(xì)胞”(Treg) 在免疫耐受和動(dòng)態(tài)平衡中起中心作用,。在這項(xiàng)研究中,，Hongbo Chi及其同事發(fā)現(xiàn),，mTORC1依賴型膽固醇生物合成對(duì)于Treg功能很重要，部分通過增加Treg“效應(yīng)子”分子CTLA4 和ICOS發(fā)揮作用,。這一發(fā)現(xiàn)說明,，在免疫信號(hào)與細(xì)胞的代謝狀態(tài)之間存在一個(gè)聯(lián)系。（生物谷Bioon.com）

生物谷推薦英文摘要：

Nature               doi: 10.1038/nature12297

mTORC1 couples immune signals and metabolic programming to establish Treg-cell function

Hu Zeng, Kai Yang, Caryn Cloer, Geoffrey Neale, Peter Vogel & Hongbo Chi

The mechanistic target of rapamycin (mTOR) pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct T-cell fate decisions. The activation of mTOR, which is the catalytic subunit of the mTORC1 and mTORC2 complexes, delivers an obligatory signal for the proper activation and differentiation of effector CD4+ T cells, whereas in the regulatory T-cell (Treg) compartment, the Akt–mTOR axis is widely acknowledged as a crucial negative regulator of Treg-cell de novo differentiation and population expansion. However, whether mTOR signalling affects the homeostasis and function of Treg cells remains largely unexplored. Here we show that mTORC1 signalling is a pivotal positive determinant of Treg-cell function in mice. Treg cells have elevated steady-state mTORC1 activity compared to naive T cells. Signals through the T-cell antigen receptor (TCR) and interleukin-2 (IL-2) provide major inputs for mTORC1 activation, which in turn programs the suppressive function of Treg cells. Disruption of mTORC1 through Treg-specific deletion of the essential component raptor leads to a profound loss of Treg-cell suppressive activity in vivo and the development of a fatal early onset inflammatory disorder. Mechanistically, raptor/mTORC1 signalling in Treg cells promotes cholesterol and lipid metabolism, with the mevalonate pathway particularly important for coordinating Treg-cell proliferation and upregulation of the suppressive molecules CTLA4 and ICOS to establish Treg-cell functional competency. By contrast, mTORC1 does not directly affect the expression of Foxp3 or anti- and pro-inflammatory cytokines in Treg cells, suggesting a non-conventional mechanism for Treg-cell functional regulation. Finally, we provide evidence that mTORC1 maintains Treg-cell function partly through inhibiting the mTORC2 pathway. Our results demonstrate that mTORC1 acts as a fundamental ‘rheostat’ in Treg cells to link immunological signals from TCR and IL-2 to lipogenic pathways and functional fitness, and highlight a central role of metabolic programming of Treg-cell suppressive activity in immune homeostasis and tolerance.