Isolating and targeting a highly active, stochastic dendritic cell subpopulation for improved immune responses.
Isolating and targeting a highly active, stochastic dendritic cell subpopulation for improved immune responses.
复制标题
DOI：
10.1016/j.celrep.2022.111563
复制
发表时间：
2022-11-01
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
通过病原体相关分子模式(PAMPs)激活的树突状细胞(DC)对于抗原递呈和适应性免疫反应的发展至关重要，但DC对PAMP信号的随机分布，特别是在免疫激活的初始阶段，人们尚不清楚。在这项研究中，我们通过对微粒(MPS)的优先吞噬分离出一个独特的DC亚群，并对这一亚群的“第一反应者”(FRS)进行了表征。我们提出的结果表明，这些细胞(1)可以通过微米级颗粒的增加和细胞表面标记的组合来分离和研究，(2)对PAMPs的反应增加，(3)通过提供初始旁分泌信号来促进适应性免疫反应，以及(4)可以被疫苗选择性地靶向调节体内的抗体和T细胞反应。这项研究对影响下游免疫反应的时间控制的、独特的细胞群提出了见解。此外，它还展示了通过FR靶向改进疫苗设计的潜力。Deak等人。以摄取微米级颗粒增加的树突状细胞亚群为特征。研究表明，“第一反应细胞”(FRs)能够产生高水平的早期炎性细胞因子，并启动先天免疫反应。通过选择性地靶向FR，他们证明了调节FR的活性可以显著改变获得性免疫反应。
Dendritic cell (DC) activation via pathogen-associated molecular patterns (PAMPs) is critical for antigen presentation and development of adaptive immune responses, but the stochastic distribution of DC responses to PAMP signaling, especially during the initial stages of immune activation, is poorly understood. In this study, we isolate a unique DC subpopulation via preferential phagocytosis of microparticles (MPs) and characterize this subpopulation of “first responders” (FRs). We present results that show these cells (1) can be isolated and studied via both increased accumulation of the micron-sized particles and combinations of cell surface markers, (2) show increased responses to PAMPs, (3) facilitate adaptive immune responses by providing the initial paracrine signaling, and (4) can be selectively targeted by vaccines to modulate both antibody and T cell responses in vivo. This study presents insights into a temporally controlled, distinctive cell population that influences downstream immune responses. Furthermore, it demonstrates potential for improving vaccine designs via FR targeting. Deak et al. characterize a dendritic cell subpopulation with increased uptake of micron-sized particles. They show that the cells, “first responders” (FRs), generate high levels of early inflammatory cytokines and initialize innate immune responses. By targeting FRs selectively, they demonstrate that modulating FR activity can drastically alter adaptive immune responses.
登录
查看更多内容
影响因子：
6.4
作者：
Collin M;Bigley V
通讯作者：
Bigley V
影响因子：
7.3
作者：
Cohn L;Delamarre L
通讯作者：
Delamarre L
影响因子：
3.7
作者：
Bausch-Fluck D;Hofmann A;Bock T;Frei AP;Cerciello F;Jacobs A;Moest H;Omasits U;Gundry RL;Yoon C;Schiess R;Schmidt A;Mirkowska P;Härtlová A;Van Eyk JE;Bourquin JP;Aebersold R;Boheler KR;Zandstra P;Wollscheid B
通讯作者：
Wollscheid B
影响因子：
14.9
作者：
Bult CJ;Blake JA;Smith CL;Kadin JA;Richardson JE;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
影响因子：
20.3
作者：
Krausgruber, Thomas;Saliba, David;Udalova, Irina A.
通讯作者：
Udalova, Irina A.