Instituto de Investigaciones Biomédicas Alberto Sols de Madrid, Consejo Superior de Investigaciones Cientificas-Universidad Autonóma de Madrid, Madrid, Spain.
Nat Immunol. 2013 Aug;14(8):831-9. doi: 10.1038/ni.2622. Epub 2013 Jun 16.
Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.
巨噬细胞是专业的吞噬细胞，能协调先天免疫反应，在不同解剖位置具有相当大的表型多样性。然而，控制组织巨噬细胞异质性的机制尚未得到很好的描述。在这里，我们发现核受体 LXRα对于脾脏边缘区（MZ）巨噬细胞的分化是必需的。LXR 缺陷小鼠在 MZ 和嗜金属巨噬细胞的产生上存在缺陷，导致对血源性抗原的异常反应。髓系特异性表达 LXRα或过继转移野生型单核细胞恢复了 LXRα缺陷小鼠的 MZ 微环境。我们的结果表明，髓系细胞中 LXRα的信号转导对于生成脾脏 MZ 巨噬细胞至关重要，并确定了核受体在生成特殊巨噬细胞亚群中的前所未有的作用。
