生物谷報道：來自美國MD安德森癌癥研究中心免疫學系,，美國國立健康研究院NIH系統(tǒng)生物學研究院等處的研究人員發(fā)現(xiàn)了不同于CD4+輔助T細胞TH1和TH2亞組的一種截然不同的亞組：THIL-17，并且進一步研究發(fā)現(xiàn)在小鼠TH17細胞中能高度表達IL-21,，從而認為IL-21是一種在TH17分化過程中必需和必要的自分泌細胞因子（autocrine cytokine）,，可以作為治療炎癥疾病的一種潛在靶標。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MD安德森癌癥研究中心免疫學系的分子免疫學與免疫調(diào)節(jié)專家董晨副教授,，其于1989年在武漢大學獲得學士學位,，之后赴美留學，目前任職安德魯癌癥中心免疫學系,。
T細胞在胸腺中成熟,，獲得其功能及學習識別自我。胸腺完成陽性選擇(讓識別抗原/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)這種選擇確切的細胞和分子機制還未完全闡明,。
從骨髓衍生的T-干細胞在胚胎發(fā)育過程移行至胸腺，在胸腺經(jīng)歷了成熟和學習識別自我,，經(jīng)胸腺的選擇,，成熟的淋巴細胞才被準許離開胸腺，可見于外周血和淋巴樣組織中,，所有成熟的T細胞僅表達CD4或CD8中的一種,。
通常將表達CD4的T細胞歸屬于輔助T細胞（helper T cell，TH）,。輔助T細胞在免疫反應(yīng)中扮演中間過程的角色：它可以增生擴散來激活其它類型的產(chǎn)生直接免疫反應(yīng)的免疫細胞,，主要表面標志是CD4。 T細胞調(diào)控或“輔助”其它淋巴細胞發(fā)揮功能,。
這些細胞可根據(jù)它們的功能,，對不同細胞因子的應(yīng)答以及分泌細胞因子的能力可再分成兩個主要部分。現(xiàn)認為TH細胞起始于能分泌IL-2的前身細胞,，經(jīng)最初的刺激,，這些細胞發(fā)育為THO細胞，它能分泌幾種細胞因子,，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.
