聚Ⅰ:C疫苗接种通过Ⅰ型和Ⅱ型干扰素信号传导促使淋巴结中B细胞滤泡附近的CXCL9短暂表达

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-08-20 DOI:10.1016/j.cyto.2024.156731
Alexander G. Ball , Katerina Morgaenko , Parastoo Anbaei , Sarah E. Ewald , Rebecca R. Pompano
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引用次数: 0

摘要

亚单位疫苗会推动淋巴结(LN)中免疫细胞与细胞之间的相互作用,但目前仍不清楚不同佐剂如何影响组织中负责这种相互作用的趋化因子。在这里,我们测试了经典 Th1 极化疫苗与其他佐剂相比在淋巴结中引发独特趋化因子特征的假设。接种多聚肌苷酸:多聚胞苷酸(Poly I:C)疫苗会导致CXCL9的动态上调,这种上调定位于小叶间区,而在接种明矾或明矾和多聚 I:C 混合疫苗后却观察不到这种反应。使用体内小鼠模型和活体外 LN 切片进行的实验表明,接种多聚 I:C 会导致 LN 中的 I 型 IFN 反应,从而分泌 IFNγ,而在这种情况下,CXCL9 的表达需要 I 型 IFN 和 IFNγ。CXCL9在LN中的表达与疫苗接种后IgG2c抗体极化相关;然而,CXCL9受体的基因耗竭并不能阻止这种极化的发生。此外,我们还测量了体内外 LN 切片在受到多种佐剂刺激后的 CXCL9 分泌情况,并证实诱导 IFNγ 反应的佐剂也能促进 CXCL9 的表达。总之,这些结果确定了一系列Th1极化佐剂中的CXCL9特征,并确定了在LN中驱动CXCL9的途径,为在未来疫苗中靶向这一趋化因子途径开辟了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling

Subunit vaccines drive immune cell–cell interactions in the lymph node (LN), yet it remains unclear how distinct adjuvants influence the chemokines responsible for this interaction in the tissue. Here, we tested the hypothesis that classic Th1-polarizing vaccines elicit a unique chemokine signature in the LN compared to other adjuvants. Polyinosinic:polycytidylic acid (Poly I:C) vaccination resulted in dynamic upregulation of CXCL9 that was localized in the interfollicular region, a response not observed after vaccination with alum or a combination of alum and poly I:C. Experiments using in vivo mouse models and live ex vivo LN slices revealed that poly I:C vaccination resulted in a type-I IFN response in the LN that led to the secretion of IFNγ, and type-I IFN and IFNγ were required for CXCL9 expression in this context. CXCL9 expression in the LN was correlated with an IgG2c antibody polarization after vaccination; however, genetic depletion of the receptor for CXCL9 did not prevent the development of this polarization. Additionally, we measured secretion of CXCL9 from ex vivo LN slices after stimulation with a variety of adjuvants and confirmed that adjuvants that induced IFNγ responses also promoted CXCL9 expression. Taken together, these results identify a CXCL9 signature in a suite of Th1-polarizing adjuvants and determined the pathway involved in driving CXCL9 in the LN, opening avenues to target this chemokine pathway in future vaccines.

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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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