Background

Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear.

Objectives

We sought to examine the function of CD163 in steady-state as well as in sterile and infectious inflammation.

Methods

Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wild-type and CD163^−/− mice.

Results

We describe a subpopulation of bone marrow–resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow–derived macrophages. Development of CD163⁺ BMRMs is strictly dependent on IFN regulatory factor-8. CD163⁺ BMRMs show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163^−/− mice show a stronger inflammation in allergic contact dermatitis, indicating a regulatory role of CD163. However, CD163^−/− mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well.

Conclusions

Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.

中文翻译：

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CD163表达定义了骨髓中特定的，依赖IRF8的免疫调节巨噬细胞。

背景

清道夫受体CD163仅在单核细胞/巨噬细胞上表达，并广泛用作交替激活的巨噬细胞的标记。但是，CD163的作用尚不清楚。

目标

我们试图检查CD163在稳态以及无菌和感染性炎症中的功能。

方法

在正常和炎性条件下，在小鼠中分析了CD163的表达。在野生型和CD163 ^-/-小鼠的炎症模型中研究了CD163的功能相关性。

结果

我们描述了以CD163的高表达为特征的骨髓驻留巨噬细胞（BMRM）的亚群，其功能不同于经典的骨髓衍生巨噬细胞。CD163 ⁺ BMRM的发育严格依赖于IFN调节因子8。CD163 ⁺ BMRMs显示特定的转录组和细胞因子分泌模式，表明这些细胞具有特定的免疫调节特性。因此，CD163 ^-/-小鼠在变应性接触性皮炎中表现出更强的炎症，表明CD163的调节作用。但是，CD163 ^-/-小鼠极易感染金黄色葡萄球菌，这也证明了CD163与抗菌素防御的相关性。

结论

我们的数据表明，抗炎和免疫抑制机制不一定与抗菌活性降低相关。相比之下，我们的数据定义了一种新型的巨噬细胞种群，其一方面控制了压倒性的炎症，但另一方面对于有效控制感染也是必需的。