EA 7501 GICC, Tours University, Tours, France.
CRCI2NA, SFR ICAT, Inserm, CNRS, Angers and Nantes University, Angers, France.
Front Immunol. 2022 Nov 1;13:1054425. doi: 10.3389/fimmu.2022.1054425. eCollection 2022.
The neonatal Fc receptor (FcRn) plays a central role in recycling and biodistributing immunoglobulin G. FcRn is also involved in many physiological immune functions as well as pathological immune responses in cancer or autoimmune diseases. Low levels of FcRn in tumor cells and the microenvironment is associated with poor prognosis in non-small cell lung cancers. Among cells that are present in the tumor microenvironment, macrophages express high levels of FcRn. Macrophages are involved in these pathophysiological contexts by their dual differentiation states of pro- or anti-inflammatory macrophages. However, variations in FcRn protein expression have not been described in macrophage subtypes. In this work, we studied FcRn expression in an model of pro- and anti-inflammatory macrophage differentiation. We demonstrated an inverse relation between FcRn protein and mRNA expression in macrophage populations. Autophagy, which is involved in protein degradation and acquisition of phagocytic function in macrophages, participated in regulating FcRn levels. Intravenous immunoglobulin protected FcRn against autophagosome degradation in anti-inflammatory macrophages. Our data demonstrate that autophagy participates in regulating FcRn expression in pro- and anti-inflammatory macrophages. This finding raises new questions concerning the regulation of FcRn in immune functions.
新生儿 Fc 受体 (FcRn) 在免疫球蛋白 G 的再循环和生物分布中发挥核心作用。FcRn 还参与许多生理免疫功能以及癌症或自身免疫性疾病中的病理免疫反应。肿瘤细胞和微环境中低水平的 FcRn 与非小细胞肺癌的预后不良相关。在肿瘤微环境中存在的细胞中，巨噬细胞表达高水平的 FcRn。巨噬细胞通过其促炎或抗炎巨噬细胞的双重分化状态参与这些病理生理环境。然而，FcRn 蛋白表达的变化在巨噬细胞亚型中尚未描述。在这项工作中，我们研究了促炎和抗炎巨噬细胞分化模型中 FcRn 的表达。我们证明了巨噬细胞群体中 FcRn 蛋白和 mRNA 表达之间呈反比关系。自噬参与巨噬细胞中蛋白质降解和吞噬功能的获得，参与调节 FcRn 水平。静脉注射免疫球蛋白可防止抗炎巨噬细胞中自噬体降解 FcRn。我们的数据表明自噬参与调节促炎和抗炎巨噬细胞中的 FcRn 表达。这一发现提出了有关免疫功能中 FcRn 调节的新问题。
