Department of Microbiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
PLoS One. 2011;6(7):e21949. doi: 10.1371/journal.pone.0021949. Epub 2011 Jul 11.
Earlier, we have shown that GM-CSF-exposed CD8α- DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1β can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1β on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1β enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1β and IL-12 had only a modest effect on Foxp3- expressing T cells; however, T cells activated in the absence of DCs but in the presence of IL-1β or IL-12 showed highly significant increase and decrease in Foxp3+ T cell frequencies respectively suggesting direct effects of these cytokines on T cells and a role for IL-1β in promoting Foxp3 expression. Importantly, purified CD4+CD25+ cells showed a significantly higher ability to maintain Foxp3 expression when activated in the presence of IL-1β. Further analyses showed that the ability of IL-1β to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-β1 and IL-2 expression in Foxp3+Tregs and CD25- effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1β enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1β can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity.
早些时候，我们已经证明，表达低水平促炎细胞因子 IL-12 和 IL-1β 的 GM-CSF 暴露的 CD8α-DC 可以诱导 Foxp3+Treg，从而抑制自身免疫。在这里，我们研究了 IL-12 和 IL-1β 在存在和不存在 DC 的情况下对 T 细胞激活时 Foxp3 表达的差异影响。外源性 IL-12 消除了，但 IL-1β 增强了 GM-CSF 暴露的耐受性 DC 促进 Foxp3 表达的能力。DC 预先暴露于 IL-1β 和 IL-12 对表达 Foxp3 的 T 细胞只有适度的影响；然而，在不存在 DC 但存在 IL-1β 或 IL-12 的情况下激活的 T 细胞显示出 Foxp3+T 细胞频率的显著增加和减少，这表明这些细胞因子对 T 细胞具有直接作用，以及 IL-1β 在促进 Foxp3 表达中的作用。重要的是，当在 IL-1β 的存在下激活时，纯化的 CD4+CD25+细胞显示出维持 Foxp3 表达的显著更高的能力。进一步的分析表明，IL-1β 维持 CD25+T 细胞中 Foxp3 表达的能力依赖于 TGF-β1 和 IL-2 在 Foxp3+Treg 和 CD25-效应器 T 细胞中的表达。IL-1β 暴露于 CD4+CD25+T 细胞增强了它们在体外抑制效应 T 细胞反应的能力，并在体内抑制正在进行的实验性自身免疫甲状腺炎。这些结果表明，IL-1β 可以帮助增强/维持 Treg，这可能在炎症期间维持外周耐受以预防和/或抑制自身免疫中发挥重要作用。
