Sironi Marina, Martinez Fernando O, D'Ambrosio Daniele, Gattorno Marco, Polentarutti Nadia, Locati Massimo, Gregorio Andrea, Iellem Andrea, Cassatella Marco A, Van Damme Jo, Sozzani Silvano, Martini Alberto, Sinigaglia Francesco, Vecchi Annunciata, Mantovani Alberto
Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Milan, Italy.
J Leukoc Biol. 2006 Aug;80(2):342-9. doi: 10.1189/jlb.1005586. Epub 2006 May 30.
CC chemokine ligand 1 (CCL1; I-309) is a CC chemokine that interacts with CC chemokine receptor 8, which is preferentially expressed in polarized T helper cell type 2 and Tc2 cells, in eosinophils, and in T regulatory cells. The present study, prompted by transcriptional profiling of human monocytes undergoing different forms of activation, was designed to characterize the production of CCL1 in monocytes compared with the production of other chemokines (CCL2, CCL22, and CCL18) differentially regulated by distinct activation signals. Lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), interleukin (IL)-1beta, tumor necrosis factor alpha, IL-4, IL-13, IL-10, IL-6, IL-18, and combinations thereof did not induce CCL1 production in monocytes, and some of these signals stimulated production of reference chemokines. Induction of CCL1 in monocytes required engagement of Fc receptor for immunoglobulin G (FcgammaR)II and exposure to IL-1beta or LPS. This combination of stimuli results in a form of M2 (M2b, Type 2) macrophage activation. FcgammaR engagement also induced CCL22 and amplified its stimulation by IL-4. In contrast, FcgammaR stimulation inhibited the IL-10- and LPS-mediated induction of CCL18. IL-10, IL-4, and IFN-gamma inhibited induction of CCL1 by FcgammaR ligation and IL-1beta. CCL1 was present in synovial fluids and macrophages in juvenile idiopathic arthritis. Thus, regulation of CCL1 in human monocytes is unique, with an obligate requirement of FcgammaR engagement and costimulation by signals (IL-1beta and LPS), which use the myeloid differentiation primary-response protein 88 adaptor protein. Thus, CCL1 is a CC chemokine with a unique pattern of regulation associated with a distinct form of M2 (Type 2, M2b) monocyte activation, which participates in macrophage-dependent regulatory circuits of innate and adaptive immunity.
CC趋化因子配体1（CCL1；I-309）是一种CC趋化因子，它与CC趋化因子受体8相互作用，该受体在极化的2型辅助性T细胞和Tc2细胞、嗜酸性粒细胞以及调节性T细胞中优先表达。本研究受经历不同激活形式的人类单核细胞转录谱分析的启发而开展，旨在比较单核细胞中CCL1的产生与其他受不同激活信号差异调节的趋化因子（CCL2、CCL22和CCL18）的产生情况，以对CCL1的产生进行特征描述。脂多糖（LPS）、干扰素-γ（IFN-γ）、白细胞介素（IL）-1β、肿瘤坏死因子α、IL-4、IL-13、IL-10、IL-6、IL-18及其组合均不能诱导单核细胞产生CCL1，其中一些信号可刺激参考趋化因子的产生。单核细胞中CCL1的诱导需要免疫球蛋白G（FcγR）II的Fc受体参与并暴露于IL-1β或LPS。这种刺激组合导致一种M2（M2b，2型）巨噬细胞激活形式。FcγR的参与还诱导了CCL22的产生，并增强了IL-4对其的刺激作用。相反，FcγR刺激抑制了IL-10和LPS介导的CCL18的诱导。IL-10、IL-4和IFN-γ抑制FcγR连接和IL-1β对CCL1的诱导。CCL1存在于幼年特发性关节炎患者的滑液和巨噬细胞中。因此，人类单核细胞中CCL1的调节是独特的，它绝对需要FcγR的参与以及信号（IL-1β和LPS）的共刺激，这些信号利用髓样分化初级反应蛋白88衔接蛋白。因此，CCL1是一种具有独特调节模式的CC趋化因子，与一种独特形式的M2（2型，M2b）单核细胞激活相关，它参与先天免疫和适应性免疫中依赖巨噬细胞的调节回路。
