CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation
CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation
复制标题
DOI：
10.1182/blood-2011-05-352682
复制
发表时间：
2011-12-01
期刊：
影响因子：
20.3
通讯作者：
van Ham, Marieke
中科院分区：
文献类型：
--
作者：
de Wit, Jelle;Souwer, Yuri;van Ham, Marieke
产生IL-17的CD4(+)T辅助细胞(Th17)对于对抗细胞外病原体和自身免疫性疾病的免疫是重要的。推动人类Th17发育的因素仍然是一个有争议的问题。在这里，我们表明，与经典的CD28共刺激相比，通过CD5或CD6淋巴细胞受体的交替共刺激形成了人类Th17启动的更好的途径。在Th17促进细胞因子IL-1β、IL-6、IL-23和转化生长因子-β的存在下，CD5共刺激诱导更多的Th17细胞产生更多的IL-17，在此之前信号转导和转录激活因子3(STAT3)是Th17分化的关键调节因子，并增加IL-17相关转录因子维甲酸相关孤儿受体-伽玛的水平。值得注意的是，这些Th17促进信号严重依赖于CD5诱导的IL-23受体(IL-23R)表达的上调。目前的数据支持一种新的概念，即通过CD5替代共刺激而不是通过CD28的经典共刺激，通过促进IL-23R的表达来启动初始T细胞以稳定Th17的发育。(血。2011；118(23)：6107-6114)
IL-17-producing CD4(+) T helper (Th17) cells are important for immunity against extracellular pathogens and in autoimmune diseases. The factors that drive Th17 development in human remain a matter of debate. Here we show that, compared with classic CD28 costimulation, alternative costimulation via the CD5 or CD6 lymphocyte receptors forms a superior pathway for human Th17-priming. In the presence of the Th17-promoting cytokines IL-1 beta, IL-6, IL-23, and transforming growth factor-beta (TGF-beta), CD5 costimulation induces more Th17 cells that produce higher amounts of IL-17, which is preceded by prolonged activation of signal transducer and activator of transcription 3 (STAT3), a key regulator in Th17 differentiation, and enhanced levels of the IL-17-associated transcription factor retinoid-related orphan receptor-gamma t (ROR-gamma t). Strikingly, these Th17-promoting signals critically depend on CD5-induced elevation of IL-23 receptor (IL-23R) expression. The present data favor the novel concept that alternative costimulation via CD5, rather than classic costimulation via CD28, primes naive T cells for stable Th17 development through promoting the expression of IL-23R. (Blood. 2011;118(23):6107-6114)