生物谷報(bào)道：來自美國(guó)MD安德森癌癥研究中心免疫學(xué)系,，美國(guó)國(guó)立健康研究院NIH系統(tǒng)生物學(xué)研究院等處的研究人員發(fā)現(xiàn)了不同于CD4+輔助T細(xì)胞TH1和TH2亞組的一種截然不同的亞組：THIL-17，并且進(jìn)一步研究發(fā)現(xiàn)在小鼠TH17細(xì)胞中能高度表達(dá)IL-21,，從而認(rèn)為IL-21是一種在TH17分化過程中必需和必要的自分泌細(xì)胞因子（autocrine cytokine）,，可以作為治療炎癥疾病的一種潛在靶標(biāo)。這一研究成果公布在Nature雜志上
文章的通訊作者之一是美國(guó)MD安德森癌癥研究中心免疫學(xué)系的分子免疫學(xué)與免疫調(diào)節(jié)專家董晨副教授,，其于1989年在武漢大學(xué)獲得學(xué)士學(xué)位,，之后赴美留學(xué)，目前任職安德魯癌癥中心免疫學(xué)系,。
T細(xì)胞在胸腺中成熟,，獲得其功能及學(xué)習(xí)識(shí)別自我。胸腺完成陽性選擇(讓識(shí)別抗原/MHC的克隆增殖,，成熟并移行至周圍)和陰性選擇(排除能將自身抗原作為異物起反應(yīng)的克隆)的雙重功能,。有關(guān)這種選擇確切的細(xì)胞和分子機(jī)制還未完全闡明,。
從骨髓衍生的T-干細(xì)胞在胚胎發(fā)育過程移行至胸腺，在胸腺經(jīng)歷了成熟和學(xué)習(xí)識(shí)別自我,，經(jīng)胸腺的選擇,，成熟的淋巴細(xì)胞才被準(zhǔn)許離開胸腺，可見于外周血和淋巴樣組織中,，所有成熟的T細(xì)胞僅表達(dá)CD4或CD8中的一種,。
通常將表達(dá)CD4的T細(xì)胞歸屬于輔助T細(xì)胞（helper T cell，TH）,。輔助T細(xì)胞在免疫反應(yīng)中扮演中間過程的角色：它可以增生擴(kuò)散來激活其它類型的產(chǎn)生直接免疫反應(yīng)的免疫細(xì)胞,，主要表面標(biāo)志是CD4。 T細(xì)胞調(diào)控或“輔助”其它淋巴細(xì)胞發(fā)揮功能,。
這些細(xì)胞可根據(jù)它們的功能,，對(duì)不同細(xì)胞因子的應(yīng)答以及分泌細(xì)胞因子的能力可再分成兩個(gè)主要部分。現(xiàn)認(rèn)為TH細(xì)胞起始于能分泌IL-2的前身細(xì)胞,，經(jīng)最初的刺激,，這些細(xì)胞發(fā)育為THO細(xì)胞，它能分泌幾種細(xì)胞因子,，包括IFN-γ,IL-2,IL-4,IL-5和IL-10,。
原始出處：
Nature 448, 480-483 (26 July 2007) | doi:10.1038/nature05969; Received 7 March 2007; Accepted 4 June 2007; Published online 20 June 2007
Essential autocrine regulation by IL-21 in the generation of inflammatory T cells
Roza Nurieva1, Xuexian O. Yang1, Gustavo Martinez1, Yongliang Zhang1, Athanasia D. Panopoulos1, Li Ma2, Kimberly Schluns1, Qiang Tian2, Stephanie S. Watowich1, Anton M. Jetten3 & Chen Dong1
Department of Immunology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA
Institute for Systems Biology, Seattle, Washington 98103, USA
Cell Biology Section, LRB, National Institutes of Health, NIEHS, Research Triangle Park, North Carolina 27709, USA
Correspondence to: Roza Nurieva1Chen Dong1 Correspondence and requests for materials should be addressed to C.D. (Email: [email protected]) or R.N. (Email: [email protected]).
After activation, CD4+ helper T (TH) cells differentiate into distinct effector subsets that are characterized by their unique cytokine expression and immunoregulatory function1, 2. During this differentiation, TH1 and TH2 cells produce interferon- and interleukin (IL)-4, respectively, as autocrine factors necessary for selective lineage commitment. A distinct TH subset, termed THIL-17, TH17 or inflammatory TH (THi), has been recently identified as a distinct TH lineage mediating tissue inflammation3, 4. TH17 differentiation is initiated by transforming growth factor- and IL-6 (refs 5–7) and reinforced by IL-23 (ref. 8), in which signal transduction and activators of transcription (STAT)3 and retinoic acid receptor-related orphan receptor (ROR)- mediate the lineage specification8, 9, 10. TH17 cells produce IL-17, IL-17F and IL-22, all of which regulate inflammatory responses by tissue cells but have no importance in TH17 differentiation11, 12, 13, 14. Here we show that IL-21 is another cytokine highly expressed by mouse TH17 cells. IL-21 is induced by IL-6 in activated T cells, a process that is dependent on STAT3 but not ROR-. IL-21 potently induces TH17 differentiation and suppresses Foxp3 expression, which requires STAT3 and ROR-, which is encoded by Rorc. IL-21 deficiency impairs the generation of TH17 cells and results in protection against experimental autoimmune encephalomyelitis. IL-21 is therefore an autocrine cytokine that is sufficient and necessary for TH17 differentiation, and serves as a target for treating inflammatory diseases.
