Inflammatory Monocytes Recruited to Allergic Skin Acquire an Anti-inflammatory M2 Phenotype via Basophil-Derived Interleukin-4
Inflammatory Monocytes Recruited to Allergic Skin Acquire an Anti-inflammatory M2 Phenotype via Basophil-Derived Interleukin-4
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DOI：
10.1016/j.immuni.2012.11.014
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发表时间：
2013-03-21
期刊：
影响因子：
32.4
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
--
作者：
Egawa, Mayumi;Mukai, Kaori;Karasuyama, Hajime
单核细胞和巨噬细胞是炎症的重要效应物和调节物，并且两者都可以基于其表型分为不同的子集。单个单核细胞亚群和巨噬细胞亚群之间的发育和功能关系尚未完全阐明，尽管通常认为Ly 6C（+）CCR 2（+）炎性单核细胞和Ly 6C（-）CCR 2（-）驻留单核细胞分别分化为M1（经典活化）和M2（替代活化）巨噬细胞。在这里，我们表明，炎症单核细胞招募到过敏性皮肤获得M2样表型响应嗜碱性粒细胞来源的白细胞介素-4（IL-4），并发挥抗炎功能。CCR 2缺陷小鼠出乎意料地表现出过敏性炎症的加重而不是减轻，尽管炎症性单核细胞向皮肤病变的募集受损。来自野生型而非IL-4受体缺陷小鼠的炎性单核细胞的连续转移抑制了CCR 2缺陷小鼠中恶化的炎症。因此，在过敏反应中，炎性单核细胞可以在嗜碱性粒细胞的影响下从促炎性转化为抗炎性。
Monocytes and macrophages are important effectors and regulators of inflammation, and both can be divided into distinct subsets based on their phenotypes. The developmental and functional relationship between individual subsets of monocytes and those of macrophages has not been fully elucidated, although Ly6C(+)CCR2(+) inflammatory and Ly6C(-)CCR2(-) resident monocytes are generally thought to differentiate into M1 (classically activated) and M2 (alternatively activated) macrophages, respectively. Here we show that inflammatory monocytes recruited to allergic skin acquired an M2-like phenotype in response to basophil-derived interleukin-4 (IL-4) and exerted an anti-inflammatory function. CCR2-deficient mice unexpectedly displayed an exacerbation rather than alleviation of allergic inflammation, in spite of impaired recruitment of inflammatory monocytes to skin lesions. Adoptive transfer of inflammatory monocytes from wild-type but not IL-4 receptor-deficient mice dampened the exacerbated inflammation in CCR2-deficient mice. Thus, inflammatory monocytes can be converted from being proinflammatory to anti-inflammatory under the influence of basophils in allergic reactions.