Interleukin-21 inhibits dendritic cell activation and maturation
Interleukin-21 inhibits dendritic cell activation and maturation
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DOI：
10.1182/blood-2003-03-0669
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发表时间：
2003-12-01
期刊：
影响因子：
20.3
通讯作者：
Rückert, R
中科院分区：
文献类型：
--
作者：
Brandt, K;Bulfone-Paus, S;Rückert, R
白介素21(IL-21)是新近发现的一种与IL-4和IL-15同源的细胞因子。它们属于一个细胞因子家族，使用共同的伽马链进行信号传递，但也有自己的高亲和力受体。由于众所周知，IL-4调节树突状细胞(DC)的分化和激活，我们比较了IL-21和IL-15对DC分化、成熟和功能的影响。在此，我们发现在IL-21(IL-21)存在的情况下，由粒细胞-巨噬细胞集落刺激因子(GMCSF)产生的DC分化为表型和功能改变的DC，其特征是主要组织相容性复合体11类(MHCH)表达减少，抗原摄取增加，体外对T细胞激活的刺激能力降低。此外，IL-21DC完全不能诱导抗原(Ag)特异性T细胞介导的接触性超敏反应。此外，IL-21可阻断脂多糖(LPS)诱导的DC的激活和成熟，这不是通过释放抗炎细胞因子IL-10来实现的。相反，当补充IL-15的GMCSF时，DC分化为成熟的抗原提呈细胞(APC)，其抗原摄取率较低，在体外和体内刺激T细胞的能力显著增强。综上所述，这些结果证实了这些结构上相关的细胞因子对DC的二分性作用，确立了IL-21作为DC激活的抑制细胞因子和IL-15作为DC功能的有力刺激因子，使这两种细胞因子成为DC诱导的免疫反应治疗操作的有趣靶点。(C)2003年，由美国血液病学会提供。
Interleukin 21 (IL-21) is a newly described cytokine with homology to IL-4 and IL-15. They belong to a cytokine family that uses the common gamma chain for signaling but also have their private high-affinity receptors. Since it is well known that IL-4 modulates differentiation and activation of dendritic cells (DCs), we analyzed effects of IL-21 compared with IL-15 on DC differentiation, maturation, and function. Here we show that DCs generated with granulocyte-macrophage colony-stimulating factor (GMCSF) in the presence of IL-21 (IL-21 DCs) differentiated into phenotypically and functionally altered DCs characterized by reduced major histocompatibility complex class 11 (MHCH) expression, high antigen uptake, and low stimulatory capacity for T-cell activation in vitro. Additionally, IL-21DCs completely failed to induce antigen (Ag)-specific T-cell mediated contact hypersensitivity. Furthermore, IL-21 blocked lipopolysaccharide (LPS)-induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10. In contrast, when supplementing GMCSF with IL-15, DCs differentiated into mature antigen-presenting cells (APCs) with low antigen uptake and highly significant increased capacities to stimulate T cells in vitro and in vivo. Taken together, these results identify a dichotomous action of these structurally related cytokines on DCs, establishing IL-21 as inhibitory cytokine on DC activation and IL-15 as potent stimulator of DC function, making both cytokines interesting targets for therapeutic manipulation of DC-induced immune reactions. (C) 2003 by The American Society of Hematology.