Type II-activated macrophages suppress the development of experimental autoimmune encephalomyelitis
Type II-activated macrophages suppress the development of experimental autoimmune encephalomyelitis
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DOI：
10.1038/icb.2008.99
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发表时间：
2009-03-01
影响因子：
4
通讯作者：
La Flamme, Anne Camille
中科院分区：
文献类型：
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作者：
Tierney, Joanna B.;Kharkrang, Marie;La Flamme, Anne Camille
用连接Fcc受体（Fc γ R）的免疫复合物治疗抑制实验性自身免疫性脑脊髓炎（EAE）的发展。为了确定作用机制，我们研究了这些免疫复合物如何影响巨噬细胞的II型活化（即在促炎环境中暴露于免疫复合物）。我们的研究结果表明，较低剂量的干扰素-γ（IFN-γ）更有效地引发骨髓源性巨噬细胞（BMM phi）产生更多的白细胞介素10（IL-10）和更少的IL-12 p40响应脂多糖（LPS）和免疫复合物相比，单独的LPS。此外，在最低水平的IFN-γ（20 U ml（-1））下，在LPS和免疫复合物刺激的巨噬细胞（即II型活化的）中观察到的CD 40、CD 80和PD-L1的表面表达显著低于仅用LPS刺激的巨噬细胞（即经典活化的）。最后，用II型活化的巨噬细胞治疗小鼠可保护其免于发生EAE，这表明免疫复合物的施用通过诱导II型活化的巨噬细胞而保护其免受EAE。
Treatment with immune complexes, which ligate Fcc receptors (Fc gamma Rs), suppresses the development of experimental autoimmune encephalomyelitis (EAE). To determine the mechanism of action, we investigated how these immune complexes affected type II activation of macrophages (that is, exposure to immune complexes in a proinflammatory environment). Our results show that lower doses of interferon-gamma (IFN-gamma) were more effective at priming bone marrow-derived macrophages (BMM phi) to produce more interleukin 10 (IL-10) and less IL-12p40 in response to lipopolysaccharide (LPS) and immune complexes compared with LPS alone. Moreover, at the lowest level of IFN-gamma (20 U ml(-1)), a significant downregulation in the surface expression of CD40, CD80 and PD-L1 was observed in LPS and immune complex-stimulated macrophages (that is, type II activated) than macrophages stimulated with LPS alone (that is, classically activated). Finally, treatment of mice with type II-activated macrophages protected them from developing EAE, suggesting that administration of immune complexes is protective against EAE by inducing type II-activated macrophages.