Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.
Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.
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DOI：
10.1016/j.cell.2017.11.034
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发表时间：
2018-01-11
期刊：
影响因子：
64.5
通讯作者：
Chavakis T
中科院分区：
文献类型：
--
作者：
Mitroulis I;Ruppova K;Wang B;Chen LS;Grzybek M;Grinenko T;Eugster A;Troullinaki M;Palladini A;Kourtzelis I;Chatzigeorgiou A;Schlitzer A;Beyer M;Joosten LAB;Isermann B;Lesche M;Petzold A;Simons K;Henry I;Dahl A;Schultze JL;Wielockx B;Zamboni N;Mirtschink P;Coskun Ü;Hajishengallis G;Netea MG;Chavakis T
训练的先天免疫促进骨髓细胞对二次攻击的持续有利反应，尽管它们在循环中的寿命很短。因此，我们假设训练的免疫通过调节造血干细胞和祖细胞（HSPC）起作用。对小鼠给予β-葡聚糖（原型训练免疫诱导激动剂）可诱导髓系祖细胞扩增，这与先天免疫介质（如IL-1β和粒细胞-巨噬细胞集落刺激因子（GM-CSF））的信号升高以及葡萄糖代谢和胆固醇生物合成的适应性变化有关。训练免疫相关的骨髓生成增加导致对二次LPS攻击的有益反应和对小鼠化疗诱导的骨髓抑制的保护。因此，骨髓中髓系祖细胞的调节是训练免疫的组成部分，迄今为止，其被认为涉及外周成熟髓系细胞的功能变化。训练的免疫（TI）调节骨髓中的造血祖细胞TI与祖细胞中细胞代谢的适应有关TI增加造血祖细胞的扩增和骨髓生成TI促进对全身性炎症和化疗的有益应答训练的免疫期间造血干细胞和祖细胞的调节允许骨髓细胞对二次攻击的持续应答，尽管它们在循环中的寿命短。
Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery. Trained immunity (TI) modulates hematopoietic progenitors in bone marrow TI is associated with adaptations in cell metabolism in progenitors TI increases expansion of hematopoietic progenitors and myelopoiesis TI promotes beneficial responses to systemic inflammation and chemotherapy Modulation of hematopoietic stem and progenitor cells during trained immunity allows a sustained response of myeloid cells to a secondary challenge despite their short lifespan in circulation.
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影响因子：
--
作者：
Musso G;Mosimann C;Panáková D;Burger A;Zhou Y;Zon LI;MacRae CA
通讯作者：
MacRae CA
影响因子：
120.7
作者：
Bonifacio, Ezio;Ziegler, Anette-G.;Achenbach, Peter
通讯作者：
Achenbach, Peter
影响因子：
7.4
作者：
Fuhrer, Tobias;Heer, Dominik;Zamboni, Nicola
通讯作者：
Zamboni, Nicola
影响因子：
29
作者：
Arts RJ;Novakovic B;Ter Horst R;Carvalho A;Bekkering S;Lachmandas E;Rodrigues F;Silvestre R;Cheng SC;Wang SY;Habibi E;Gonçalves LG;Mesquita I;Cunha C;van Laarhoven A;van de Veerdonk FL;Williams DL;van der Meer JW;Logie C;O'Neill LA;Dinarello CA;Riksen NP;van Crevel R;Clish C;Notebaart RA;Joosten LA;Stunnenberg HG;Xavier RJ;Netea MG
通讯作者：
Netea MG
影响因子：
100.3
作者：
Goodridge, Helen S.;Ahmed, S. Sohail;Wilson, Christopher B.
通讯作者：
Wilson, Christopher B.