小柯机器人

德国埃尔兰根-纽伦堡弗里德里希-亚历山大大学Falk Nimmerjahn团队近期取得重要工作进展，他们研究发现，免疫球蛋白G依赖的炎性骨重塑抑制需要模式识别受体Dectin-1。相关研究成果2023年3月21日在线发表于《免疫》杂志上。

据介绍，免疫球蛋白G（IgG）抗体是感染性和自身免疫性疾病中炎症的主要驱动因素。然而，在合血清IgG（IVIg）中，抗体具有强大的免疫调节和抗炎活性，但它们是如何介导的尚不清楚。

研究人员探讨了细胞因子和自身抗体驱动的类风湿性关节炎模型中IgG依赖性炎症消退的启动，发现IVIg唾液酸化抑制关节炎症，而破骨细胞生成的抑制是与唾液酸无关的。相反，在缺乏受体Dectin-1或FcγRIIb的小鼠中，IVIg依赖性的破骨细胞生成抑制被消除。原子分子动力学模拟和超分辨率显微显示，Dectin-1促进了FcγRIIb膜构象，使IgG能够有效结合，并增强了与小鼠和人类IgG亚类的相互作用。IVIg通过需要Dectin-1的FcγRIIb依赖性信号对单核细胞进行重编程。

总之，这一数据确定了Dectin-1作为IgG依赖性抑制小鼠和人类破骨细胞生成的共同抑制检查点的病原体独立性功能。这些发现可能对自身抗体和细胞因子驱动的炎症的治疗靶向性有意义。

附：英文原文

Title: Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1

Author: Michaela Seeling, Matthias Phnl, Sibel Kara, Nathalie Horstmann, Carolina Riemer, Miriam Whner, Chunguang Liang, Christin Brückner, Patrick Eiring, Anja Werner, Markus Biburger, Leon Altmann, Martin Schneider, Lukas Amon, Christian H.K. Lehmann, Sooyeon Lee, Meik Kunz, Diana Dudziak, Georg Schett, Tobias Buerle, Anja Lux, Jan Tuckermann, Timo Vgtle, Bernhardt Nieswandt, Markus Sauer, Rainer A. Bckmann, Falk Nimmerjahn

Issue&Volume: 2023-03-21

Abstract: Immunoglobulin G (IgG) antibodies are major drivers of inflammation during infectious and autoimmune diseases. In pooled serum IgG (IVIg), however, antibodies have a potent immunomodulatory and anti-inflammatory activity, but how this is mediated is unclear. We studied IgG-dependent initiation of resolution of inflammation in cytokine- and autoantibody-driven models of rheumatoid arthritis and found IVIg sialylation inhibited joint inflammation, whereas inhibition of osteoclastogenesis was sialic acid independent. Instead, IVIg-dependent inhibition of osteoclastogenesis was abrogated in mice lacking receptors Dectin-1 or FcγRIIb. Atomistic molecular dynamics simulations and super-resolution microscopy revealed that Dectin-1 promoted FcγRIIb membrane conformations that allowed productive IgG binding and enhanced interactions with mouse and human IgG subclasses. IVIg reprogrammed monocytes via FcγRIIb-dependent signaling that required Dectin-1. Our data identify a pathogen-independent function of Dectin-1 as a co-inhibitory checkpoint for IgG-dependent inhibition of mouse and human osteoclastogenesis. These findings may have implications for therapeutic targeting of autoantibody and cytokine-driven inflammation.

DOI: 10.1016/j.immuni.2023.02.019

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00093-6

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