Inui Masanori, Tazawa Kino, Kishi Yoshiro, Takai Toshiyuki
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Medical & Biological Laboratories, Co., Ltd., 4-5-3, Sakae, Naka-ku, Nagoya, 460-0008, Japan.
BMC Immunol. 2015 Apr 21;16:20. doi: 10.1186/s12865-015-0086-z.
Monocytes and macrophages produce interleukin (IL)-10, an immunoregulatory cytokine and a potent therapeutic tool for immune disorders. Augmentation of IL-10 production with a concomitant reduction of proinflammatory cytokines in macrophages in vitro is attained by doubly stimulating the cells with a toll-like receptor ligand and immunoglobulin (Ig)G immune complexes, a response known as that of regulatory (or alternatively activated/M2) macrophages. However, it has not been explored sufficiently how such a regulatory response could be exploited for anti-inflammation. Our objective is to find a potential way or condition for augmenting IL-10 by monocytes/macrophages in vivo and in vitro.
We show that platelets, when they are opsonized with IgG, can convert human peripheral blood circulating monocytes to IL-10-producing regulatory monocytes in vitro and also in a murine in vivo model. Co-culturing of platelets and monocytes in the presence of anti-integrin IgG and a bacterial lipopolysaccharide augmented IL-10 production via a direct interaction between platelets and monocytes. This novel way of enhancing IL-10 was mediated by activating-type Fc receptors for IgG.
These findings indicate that the IgG-bound platelet-induced conversion of monocytes to regulatory cells might provide a novel strategy for controlling inflammation.
单核细胞和巨噬细胞可产生白细胞介素（IL）-10，这是一种免疫调节细胞因子，也是治疗免疫紊乱的有效工具。在体外，通过用Toll样受体配体和免疫球蛋白（Ig）G免疫复合物双重刺激巨噬细胞，可实现IL-10产生增加，同时促炎细胞因子减少，这种反应被称为调节性（或替代性活化/M2）巨噬细胞的反应。然而，尚未充分探索如何利用这种调节反应来进行抗炎。我们的目标是找到一种在体内和体外增强单核细胞/巨噬细胞产生IL-10的潜在方法或条件。
我们发现，当血小板用IgG调理后，可在体外以及小鼠体内模型中将人外周血循环单核细胞转化为产生IL-10的调节性单核细胞。在抗整合素IgG和细菌脂多糖存在的情况下，血小板与单核细胞共培养可通过血小板与单核细胞之间的直接相互作用增强IL-10的产生。这种增强IL-10的新方法是由IgG的活化型Fc受体介导的。
这些发现表明，IgG结合的血小板诱导单核细胞转化为调节性细胞可能为控制炎症提供一种新策略。
