Nature：华人教授解析免疫学突破性进展
生物谷报道：来自美国MD安德森癌症研究中心免疫学系，美国国立健康研究院NIH系统生物学研究院等处的研究人员发现了不同于CD4+辅助T细胞TH1和TH2亚组的一种截然不同的亚组：THIL-17，并且进一步研究发现在小鼠TH17细胞中能高度表达IL-21，从而认为IL-21是一种在TH17分化过程中必需和必要的自分泌细胞因子（autocrine cytokine），可以作为治疗炎症疾病的一种潜在靶标。这一研究成果公布在Nature杂志上
文章的通讯作者之一是美国MD安德森癌症研究中心免疫学系的分子免疫学与免疫调节专家董晨副教授，其于1989年在武汉大学获得学士学位，之后赴美留学，目前任职安德鲁癌症中心免疫学系。
T细胞在胸腺中成熟，获得其功能及学习识别自我。胸腺完成阳性选择(让识别抗原/MHC的克隆增殖，成熟并移行至周围)和阴性选择(排除能将自身抗原作为异物起反应的克隆)的双重功能。有关这种选择确切的细胞和分子机制还未完全阐明。
从骨髓衍生的T-干细胞在胚胎发育过程移行至胸腺，在胸腺经历了成熟和学习识别自我，经胸腺的选择，成熟的淋巴细胞才被准许离开胸腺，可见于外周血和淋巴样组织中，所有成熟的T细胞仅表达CD4或CD8中的一种。
通常将表达CD4的T细胞归属于辅助T细胞（helper T cell，TH）。辅助T细胞在免疫反应中扮演中间过程的角色：它可以增生扩散来激活其它类型的产生直接免疫反应的免疫细胞，主要表面标志是CD4。 T细胞调控或“辅助”其它淋巴细胞发挥功能。
这些细胞可根据它们的功能，对不同细胞因子的应答以及分泌细胞因子的能力可再分成两个主要部分。现认为TH细胞起始于能分泌IL-2的前身细胞，经最初的刺激，这些细胞发育为THO细胞，它能分泌几种细胞因子，包括IFN-γ,IL-2,IL-4,IL-5和IL-10。
原始出处：
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: cdong@mdanderson.org) or R.N. (Email: rnurieva@mdanderson.org).
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.
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