調(diào)節(jié)性T細胞又稱為抑制型T細胞,，它在免疫系統(tǒng)復(fù)雜的調(diào)控機制中扮演了相當(dāng)重要的角色,。如今,，研究人員發(fā)現(xiàn)了一種阻止調(diào)節(jié)性T細胞生產(chǎn)和功能的抑制信號環(huán)路,，新成果發(fā)表在日前在線出版的《自然—免疫學(xué)》期刊上,。
人體的免疫反應(yīng)既要能迅速活化以抵御外來抗原的侵入,，又要避免過度活化造成自身組織器官的損害,，這是一個相當(dāng)精致的平衡過程,，調(diào)節(jié)性T細胞在其中發(fā)揮了重要作用，它通過抑制不需要的免疫反應(yīng)來阻止自體免疫性疾病的發(fā)生,，如糖尿病,。
Hongbo Chi和同事發(fā)現(xiàn)，受體S1P1是這些調(diào)節(jié)性T細胞的關(guān)鍵抑制劑,。在缺失S1P1的小鼠體內(nèi),，調(diào)節(jié)性T細胞的數(shù)量增加了，它們具有更大的抑制性,。相反,，過度表達S1P1的小鼠出現(xiàn)了自體免疫疾病，因為調(diào)節(jié)T細胞基本上被消滅了,。
這些最新的研究成果在臨床上有相當(dāng)?shù)闹匾?，因為目前有試驗因其他原因而正在對S1P1的功能進行調(diào)控。新研究發(fā)現(xiàn)了通過信號通道影響調(diào)節(jié)性T細胞的受體,，拓展了我們對S1P1功能的認識,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology 10, 769 - 777 (2009) 31 May 2009 | doi:10.1038/ni.1743
The receptor S1P1 overrides regulatory T cell–mediated immune suppression through Akt-mTOR
Guangwei Liu1, Samir Burns1, Gonghua Huang1, Kelli Boyd2, Richard L Proia3, Richard A Flavell4,5 & Hongbo Chi1,5
Regulatory T cells (Treg cells) are critically involved in maintaining immunological tolerance, but this potent suppression must be 'quenched' to allow the generation of adaptive immune responses. Here we report that sphingosine 1-phosphate (S1P) receptor type 1 (S1P1) delivers an intrinsic negative signal to restrain the thymic generation, peripheral maintenance and suppressive activity of Treg cells. Combining loss- and gain-of-function genetic approaches, we found that S1P1 blocked the differentiation of thymic Treg precursors and function of mature Treg cells and affected Treg cell–mediated immune tolerance. S1P1 induced selective activation of the Akt-mTOR kinase pathway to impede the development and function of Treg cells. Dynamic regulation of S1P1 contributed to lymphocyte priming and immune homeostasis. Thus, by antagonizing Treg cell–mediated immune suppression, the lipid-activated S1P1-Akt-mTOR pathway orchestrates adaptive immune responses.
1 Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
2 Animal Resources Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
3 Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
4 Howard Hughes Medical Institute, New Haven, Connecticut, USA.
5 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
