近日，來自美國弗吉尼亞大學的研究人員發(fā)現(xiàn),，絡氨酸磷酸酶SHP-1能夠抑制Th17細胞的發(fā)育,。他們表示，SHP-1也許能夠成為一個新的治療靶點來控制體內(nèi)Th17的發(fā)育,。
輔助性T細胞17(T help cell 17, Th17)是一種新發(fā)現(xiàn)的CD4+輔助T細胞亞群,，它能夠分泌促炎因子白細胞介素17（IL-17）。Th17細胞在機體防御反應中具有重要的意義,，除了能夠促進清除體內(nèi)的致病微生物,，同時也參與了自身免疫疾病的發(fā)生。
他們發(fā)現(xiàn)，絡氨酸磷酸酶SHP-1能夠作為一個重要的調(diào)節(jié)因子來調(diào)節(jié)Th17的發(fā)育,，該調(diào)節(jié)過程利用了3個補充途經(jīng),。
有趣的是，通過基因敲除SHP-1,，或是轉(zhuǎn)基因表達一個誘導的顯性負性的SHP-1,，或者是用藥物抑制SHP-1的活性，都能夠強烈的促進Th17的發(fā)育,。
分析離體的Th17,，他們發(fā)現(xiàn)在T細胞內(nèi)，利用遺傳方法或是藥物來破壞SHP-1活性會導致T細胞能夠強烈應答于IL-6及IL-21的刺激,，促進了Th17的發(fā)育,。
而且，在初始CD4+ T細胞,，SHP-1能夠減少細胞因子誘導的STAT3的磷酸化,。
總的來說，該研究表明SHP-1通過調(diào)節(jié)STAT3信號,，調(diào)節(jié)了IL-6及IL-21誘導的Th17的發(fā)育,。（生物谷Deepblue編譯）
doi: 10.1182/blood-2011-09-377069
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PMID:
The tyrosine phosphatase SHP-1 dampens murine Th17 development
Ileana S. Mauldin, Kenneth S. Tung, and Ulrike M. Lorenz.
Th17 cells represent a subset of CD4+ T helper cells that secrete the proinflammatory cytokine IL-17.Th17 cells have been ascribed both a beneficial role in promoting clearance of pathogenic fungi and bacteria, and a pathogenic role in autoimmune diseases.Here we identify the tyrosine phosphatase SHP-1 as a critical regulator of Th17 development, using 3 complementary approaches. Impaired SHP-1 activity through genetic deletion of SHP-1, transgenic expression of an inducible dominant negative SHP-1, or pharmacologic inhibition of SHP-1 strongly promotes the development of Th17.Ex vivo Th17 skewing assays demonstrate that genetic or pharmacologic disruption of SHP-1 activity in T cells results in a hyper-response to stimulation via IL-6 and IL-21, 2 cytokines that promote Th17 development.
Mechanistically, we find that SHP-1 decreases the overall cytokine-induced phosphorylation of STAT3 in primary CD4+ T cells.These data identify SHP-1 as a key modifier of IL-6–and IL-21–driven Th17 development via regulation of STAT3 signaling and suggest SHP-1 as a potential new therapeutic target for manipulating Th17 differentiation in vivo.
