气候变化领域集成服务门户(CCPortal): Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin

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DOI	10.1073/pnas.2019798118
	Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin
	Lin X.; Twelkmeyer T.; Zhu D.; Zhang L.; Zhao Y.; Zhang C.; Iwakura Y.; Meng G.; Hua Z.; Yan B.; Liu W.J.; Luo Z.; Gong S.; Chen H.; Li S.; Hou B.; Tang H.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Hepatitis B virus (HBV) vaccines are composed of surface antigen HBsAg that spontaneously assembles into subviral particles. Factors that impede its humoral immunity in 5% to 10% of vaccinees remain elusive. Here, we showed that the low-level interleukin-1 receptor antagonist (IL-1Ra) can predict antibody protection both in mice and humans. Mechanistically, murine IL-1Ra–inhibited T follicular helper (Tfh) cell expansion and subsequent germinal center (GC)-dependent humoral immunity, resulting in significantly weakened protection against the HBV challenge. Compared to soluble antigens, HBsAg particle antigen displayed a unique capture/uptake and innate immune activation, including IL-1Ra expression, preferably of medullary sinus macrophages. In humans, a unique polymorphism in the RelA/ p65 binding site of IL-1Ra enhancer associated IL-1Ra levels with ethnicity-dependent vaccination outcome. Therefore, the differential IL-1Ra response to particle antigens probably creates a suppressive milieu for Tfh/GC development, and neutralization of IL-1Ra would resurrect antibody response in HBV vaccine nonresponders. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	GC; IL-1Ra; Medullary sinus macrophage; Particle antigens; Tfh
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179749
作者单位	Institut Pasteur of Shanghai, Guangzhou Women and Children’s Medical Center, Joint Center for Infection and Immunity, Chinese Academy of Sciences, Shanghai, 200031, China; Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China; The Joint Program in Infection and Immunity, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, China; Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; The Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Shandong Center for Disease Control and Prevention, Jinan, 250014, China; Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, 278-0022, Japan; University o...
推荐引用方式 GB/T 7714	Lin X.,Twelkmeyer T.,Zhu D.,et al. Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin[J],2021,118(17).
APA	Lin X..,Twelkmeyer T..,Zhu D..,Zhang L..,Zhao Y..,...&Tang H..(2021).Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Lin X.,et al."Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).