美国斯坦福大学Taia T. Wang研究组发现，唾液酸化IgG通过诱导肺泡巨噬细胞中的转录因子REST，来保护宿主免受肺部炎症和严重流感疾病的影响。2024年11月13日，《免疫》杂志在线发表了这项成果。

研究人员发现富含唾液酸化免疫球蛋白G（IgG），而非去唾液酸化IgG，能预测人类轻度流感病程，并在小鼠挑战模型中对异源流感病毒具有广泛的保护作用。

机制研究表明，唾液酸化IgG通过诱导转录因子抑制因子元素-1沉默转录因子（REST）来介导这种保护作用。REST抑制了核因子κB（NF-κB）驱动的反应，从而防止了严重的肺部炎症，并保护了流感感染期间的肺功能。

在临床开发中的重组唾液酸化Fc分子进行治疗性给药时，类似地激活了REST，并对严重流感病程起到了保护作用，表明该通路可以在临床中加以利用。总体而言，通过唾液酸化IgG信号途径诱导REST，是限制由抗原性不同的流感毒株引起的感染性疾病继发症的策略。

据介绍，尽管大多数呼吸道病毒感染会在对宿主危害较小的情况下自行缓解，但当感染触发异常的炎症反应并损害肺部组织时，严重症状便会出现。病毒引起的肺部炎症的宿主调节因子尚未得到很好的定义。

附：英文原文

Title: Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease

Author: Saborni Chakraborty, Bowie Yik-Ling Cheng, Desmond L. Edwards, Joseph C. Gonzalez, David Kung-Chun Chiu, Hong Zheng, Courtney Scallan, Xinrong Guo, Gene S. Tan, Greg P. Coffey, Pamela B. Conley, Patrick S. Hume, William J. Janssen, Derek E. Byers, Philip A. Mudd, Jeffery Taubenberger, Matthew Memoli, Mark M. Davis, Katrin F. Chua, Michael S. Diamond, Evangelos Andreakos, Purvesh Khatri, Taia T. Wang

Issue&Volume: 2024-11-13

Abstract: While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains.

DOI: 10.1016/j.immuni.2024.10.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00482-5