必须适当调节和终止感染诱导的T细胞应答以防止免疫病理。使用转基因小鼠,我们证明,在弓形虫急性感染期间,抑制炎症需要T细胞固有的STAT1信号传导.具体来说,我们报道,在T细胞中选择性缺乏STAT1的小鼠排出寄生虫,但最终死于致死性免疫病理,其特征是异常的Th1型应答,IL-10减少和IL-13产生增加.我们还发现,与STAT1不同,在急性弓形虫病期间,STAT3对于IL-10的诱导或IL-13的抑制是不需要的.这些发现中的每一个都在体外得到了证实,ChIP-seq数据挖掘表明STAT1和STAT3共定位在Il10基因座,以及编码调节IL-10产生的其他转录因子的基因座,最著名的是Maf和Irf4。这些数据促进了对如何管理感染诱导的T细胞反应以预防免疫病理的基本理解,并提供了对STAT1抗炎特性的具体见解,突出了其在塑造Th1型反应特征中的作用。
Infection-induced T cell responses must be properly tempered and terminated to prevent immuno-pathology. Using transgenic mice, we demonstrate that T cell intrinsic STAT1 signaling is required to curb inflammation during acute infection with Toxoplasma gondii. Specifically, we report that mice lacking STAT1 selectively in T cells expel parasites but ultimately succumb to lethal immuno-pathology characterized by aberrant Th1-type responses with reduced IL-10 and increased IL-13 production. We also find that, unlike STAT1, STAT3 is not required for induction of IL-10 or suppression of IL-13 during acute toxoplasmosis. Each of these findings was confirmed in vitro and ChIP-seq data mining showed that STAT1 and STAT3 co-localize at the Il10 locus, as well as loci encoding other transcription factors that regulate IL-10 production, most notably Maf and Irf4. These data advance basic understanding of how infection-induced T cell responses are managed to prevent immuno-pathology and provide specific insights on the anti-inflammatory properties of STAT1, highlighting its role in shaping the character of Th1-type responses.