來(lái)自上海葛蘭素史克研究中心與美國(guó)Baylor醫(yī)學(xué)院的科學(xué)家最近在Th17的研究方面取得新的進(jìn)展,，相關(guān)成果文章公布在最新一期的Nature Medicine上,。
2005年Th17概念提出，由于其表達(dá)的細(xì)胞因子和生物學(xué)功能,、分化過(guò)程完全不同于Th1、Th2細(xì)胞,，且Th17在慢性感染和自體免疫疾病過(guò)程中發(fā)揮重要的作用,，因此，一經(jīng)發(fā)現(xiàn)Th17就引起了研究者們濃厚的興趣,。
Th17細(xì)胞能夠分泌產(chǎn)生IL-17A,、IL-17F、IL-6以及腫瘤壞死因子α(tumor necrosis factor α,，TNF-α)等,，其功能主要就體現(xiàn)在它分泌的這些細(xì)胞因子集體動(dòng)員、募集及活化中性粒細(xì)胞的能力上,。Th17細(xì)胞產(chǎn)生的最重要的效應(yīng)因子是IL-17,， 其受體在體內(nèi)廣泛表達(dá),。雖然Th17細(xì)胞在自身免疫病中的病理性作用得到了證實(shí),， 但研究者們認(rèn)為這并不是它們的主要的原始功能。當(dāng)出現(xiàn)感染或炎癥等嚴(yán)重傷害的早期,，機(jī)體都需要中性粒細(xì)胞參與阻止組織壞死或者膿血癥,。而Th17細(xì)胞產(chǎn)生的IL-17能有效地介導(dǎo)中性粒細(xì)胞動(dòng)員的興奮過(guò)程,，從而有效地介導(dǎo)了前炎癥反應(yīng)。
研究發(fā)現(xiàn),，過(guò)量的Th17細(xì)胞會(huì)引發(fā)嚴(yán)重的自體免疫疾病,，比如多發(fā)性硬化癥（multiple sclerosis）。了解Th17在自體免疫疾病的發(fā)生發(fā)展過(guò)程中的作用機(jī)制對(duì)治療自體免疫疾病具有重要的意義,。
Jingwu Zhang等人發(fā)現(xiàn),，一種關(guān)鍵的細(xì)胞因子IL-7是維持Th17細(xì)胞存活與擴(kuò)撒的關(guān)鍵因子。他們研究發(fā)現(xiàn),，用IL-7受體拮抗劑可有效地抑制多發(fā)性硬化癥的發(fā)病過(guò)程,，經(jīng)過(guò)IL-7受體拮抗劑的應(yīng)用，過(guò)量的Th17細(xì)胞更易進(jìn)入凋亡狀態(tài),，有助減少有害的Th17細(xì)胞,。
研究人員深入地分析IL-7與IL-7R（IL-7 receptor）對(duì)Th17發(fā)育的關(guān)鍵機(jī)制。他們發(fā)現(xiàn),，患有實(shí)驗(yàn)性自身免疫性腦脊髓炎的小鼠與患有多發(fā)性硬化癥的人類在接受IL-7后Th17細(xì)胞的數(shù)量顯著增多,。
而，對(duì)小鼠或是人類給予IL-7R拮抗劑治療后,，分化后的Th17細(xì)胞變得更易進(jìn)入細(xì)胞凋亡程序,，這可有效地緩解自體免疫疾病的發(fā)展過(guò)程。
研究者還發(fā)現(xiàn)IL-7對(duì)其他類型的輔助性T細(xì)胞和調(diào)節(jié)性T細(xì)胞沒(méi)有類似的功效,。
研究者認(rèn)為,，IL-7可能是治療多發(fā)性硬化癥的一個(gè)潛在靶位。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Medicine 10 January 2010 | doi:10.1038/nm.2077
Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease
Xuebin Liu1, Stewart Leung1, Chunxia Wang1, Zhu Tan1, Ji Wang1, Taylor B Guo1, Lei Fang1, Yonggang Zhao1, Bing Wan1, Xia Qin1, Limin Lu1, Runsheng Li1, Heng Pan1, Mingjuan Song1, Ailian Liu1, Jian Hong2, Hongtao Lu1 & Jingwu Z Zhang1
Interleukin-7 receptor (IL-7R) is genetically associated with susceptibility to multiple sclerosis. Here we describe that IL-7 is essential for survival and expansion of pathogenic T helper type 17 (TH17) cells in experimental autoimmune encephalomyelitis (EAE). IL-7 directly expanded effector TH17 cells in EAE and human TH17 cells from subjects with multiple sclerosis, whereas it was not required for TH17 differentiation. IL-7R antagonism rendered differentiated TH17 cells susceptible to apoptosis through the inhibition of Janus kinase–signal transducer and activator of transcription-5 (JAK-STAT5) pathway and altered expression of the prosurvival protein Bcl-2 and the proapoptotic protein Bax, leading to decreased severity of EAE. In contrast, TH1 and regulatory T (Treg) cells were less susceptible to or not affected by IL-7R antagonism in vivo. The selectivity was attributable to minimal expression of IL-7Rα in Treg cells and correlated with a high level of Socs1 (encoding suppressor of cytokine signaling-1) expression in TH1 cells. The study reveals a unique, previously undescribed role of IL-7–IL-7R in TH17 cell survival and expansion and has implications in the treatment of autoimmune disease.
1 Department of Neuroimmunology, GlaxoSmithKline Research and Development Center, Shanghai, China.
2 Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
