Chomarat P, Banchereau J, Davoust J, Palucka A K
Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204, USA.
Nat Immunol. 2000 Dec;1(6):510-4. doi: 10.1038/82763.
Monocytes can give rise to either antigen presenting dendritic cells (DCs) or scavenging macrophages. This differentiation is initiated when monocytes cross the endothelium. But the regulation of DC and macrophage differentiation in tissues remains elusive. When stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), monocytes yield DCs. However, we show here that the addition of fibroblasts switches differentiation to macrophages. On contact with monocytes, fibroblasts release IL-6, which up-regulates the expression of functional M-CSF receptors on monocytes. This allows the monocytes to consume their autocrine M-CSF. Thus, the interplay between IL-6 and M-CSF switches monocyte differentiation to macrophages rather than DCs, and IL-6 is an essential factor in the molecular control of antigen presenting cell development.
单核细胞可分化为抗原呈递树突状细胞(DCs)或清除性巨噬细胞。当单核细胞穿过内皮时,这种分化就开始了。但组织中DC和巨噬细胞分化的调控机制仍不清楚。当受到粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)刺激时,单核细胞会产生DCs。然而,我们在此表明,添加成纤维细胞会使分化转向巨噬细胞。成纤维细胞与单核细胞接触时会释放IL-6,IL-6会上调单核细胞上功能性M-CSF受体的表达。这使得单核细胞能够摄取其自分泌的M-CSF。因此,IL-6和M-CSF之间的相互作用将单核细胞分化转向巨噬细胞而非DCs,并且IL-6是抗原呈递细胞发育分子控制中的一个关键因素。