Gao Xiaoling, Zhao Lei, Wang Shuhe, Yang Jie, Yang Xi
Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Mol Med. 2013 Nov 8;19(1):346-56. doi: 10.2119/molmed.2013.00035.
An association between inducible costimulator ligand (ICOS-L) expression and interleukin (IL)-10 production by dendritic cells (DCs) has been commonly found in infectious disease. DCs with higher ICOS-L expression and IL-10 production are reportedly more efficient in inducing regulatory T cells (Tregs). Here we use the Chlamydia muridarum (Cm) lung infection model in IL-10 knockout (KO) mice to test the relationship between IL-10 production and ICOS-L expression by DCs. We examined ICOS-L expression, the development of T-cell subsets, including Treg, Th17 and Th1 cell, in the background of IL-10 deficiency and its relationship with ICOS-L/ICOS signaling after infection. Surprisingly, we found that the IL-10 KO mice exhibited significantly higher ICOS-L expression by DCs. Moreover, IL-10 KO mice showed lower Tregs but higher Th17 and Th1 responses, but only the Th17 response depended on ICOS signaling. Consistently, most of the Th17 cells were ICOS⁺, whereas most of the Th1 cells were ICOS⁻ in the infected mice. Furthermore, neutralization of IL-17 in IL-10 KO mice significantly exacerbated lung infection. The data suggest that ICOS-L expression on DC may be negatively regulated by IL-10 and that ICOS-L expression on DC in the presence or absence of IL-10 costimulation may promote Treg or Th17 response, without significant impact on Th1.
在传染病中，通常发现树突状细胞（DC）的诱导性共刺激分子配体（ICOS-L）表达与白细胞介素（IL）-10产生之间存在关联。据报道，ICOS-L表达较高且产生IL-10的DC在诱导调节性T细胞（Treg）方面更有效。在此，我们使用IL-10基因敲除（KO）小鼠的鼠衣原体（Cm）肺部感染模型，来测试DC产生IL-10与ICOS-L表达之间的关系。我们在IL-10缺乏的背景下，研究了ICOS-L表达、包括Treg、Th17和Th1细胞在内的T细胞亚群的发育，以及感染后其与ICOS-L/ICOS信号传导的关系。令人惊讶的是，我们发现IL-10 KO小鼠的DC表现出显著更高的ICOS-L表达。此外，IL-10 KO小鼠的Treg较低，但Th17和Th1反应较高，但只有Th17反应依赖于ICOS信号传导。一致的是，在感染的小鼠中，大多数Th17细胞是ICOS⁺，而大多数Th1细胞是ICOS⁻。此外，在IL-10 KO小鼠中中和IL-17会显著加重肺部感染。数据表明，DC上的ICOS-L表达可能受到IL-10的负调控，并且在存在或不存在IL-10共刺激的情况下，DC上的ICOS-L表达可能促进Treg或Th17反应，而对Th1没有显著影响。
