O'Shea John J, Steward-Tharp Scott M, Laurence Arian, Watford Wendy T, Wei Lai, Adamson Adewole S, Fan Samuel
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Microbes Infect. 2009 Apr;11(5):599-611. doi: 10.1016/j.micinf.2009.04.007. Epub 2009 Apr 18.
The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been notably shaken by the discovery of a third lineage of cells that selectively produce interleukin (IL)-17. Characterization of this new subset, referred to as Th17, has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Additionally, the discovery of this T cell subset has offered a fresh look at such concepts as lineage commitment and terminal differentiation. The transcriptional regulatory events and epigenetic modifications that control these processes are diverse and complex, and despite the rapid pace at which data continue to accumulate, many questions remain to be answered. Here we review our current understanding of the signaling pathways, molecular interactions and transcriptional events that lead to Th17 differentiation and effector function, as well as the epigenetic modifications that accompany them.
效应性辅助性T细胞分化为Th1或Th2谱系的范式,因发现了选择性产生白细胞介素(IL)-17的第三种细胞谱系而受到显著冲击。对这个称为Th17的新亚群的特性描述,为免疫调节、宿主防御和自身免疫性疾病的发病机制提供了令人兴奋的新见解。此外,这个T细胞亚群的发现,让人们对谱系定向和终末分化等概念有了新的认识。控制这些过程的转录调控事件和表观遗传修饰多样且复杂,尽管数据仍在迅速积累,但仍有许多问题有待解答。在这里,我们综述了目前对导致Th17分化和效应功能的信号通路、分子相互作用和转录事件,以及与之伴随的表观遗传修饰的理解。