Divergent Effects of Interleukin-4 and Interferon-γ on Macrophage-Derived Chemokine Production: An Amplification Circuit of Polarized T Helper 2 Responses

作者：Raffaella Bonecchi, Silvano Sozzani, Johnny T. Stine, Walter Luini, Giovanna D’Amico, Paola Allavena, David Chantry, Alberto Mantovani · 发表于：Blood · 年份：1998 · DOI：10.1182/blood.v92.8.2668 · 被引用次数：205 · 研究领域：Chemokine receptors and signaling、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-gamma. IFN-gamma also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-gamma and on the selectivity of this chemokine for polarized Th2 cells.