CD11c regulates neutrophil maturation.
CD11c regulates neutrophil maturation.
复制标题
DOI：
10.1182/bloodadvances.2022007719
复制
发表时间：
2023-04-11
期刊：
影响因子：
7.5
通讯作者：
Yuki, Koichi
中科院分区：
文献类型：
--
作者：
Hou, Lifei;Voit, Richard A.;Shibamura-Fujiogi, Miho;Koutsogiannaki, Sophia;Li, Yunan;Chen, Yue;Luo, Hongbo;Sankaran, Vijay G.;Yuki, Koichi
CD11c 在发育中的中性粒细胞的细胞内成分中高度表达。 CD11c 调节发育中的中性粒细胞的存活和增殖。脓毒症仍然与高发病率和死亡率相关。目前，脓毒症仅得到保守治疗。在脓毒症中，需要大量的中性粒细胞，导致中性粒细胞产生加速。未成熟的中性粒细胞被释放到循环系统中以满足需求，尽管它们在消灭微生物方面的功能较差。尽管提供更成熟的中性粒细胞的干预措施可能作为脓毒症的潜在治疗方法，但中性粒细胞分化和成熟的机制仍然知之甚少。我们发现传统上称为树突状细胞标记物的 CD11c 在中性粒细胞中表达，并调节中性粒细胞的成熟和效应功能。在缺乏 CD11c 的情况下，骨髓中的中性粒细胞成熟受到损害，同时前中性粒细胞的增殖和凋亡显着增加，与效应功能减弱相关。在脂多糖攻击下，CD11c 缺陷会诱导骨髓中出现中性粒细胞产生，从而导致未成熟中性粒细胞过度释放到循环中，与前中性粒细胞的显着增殖和凋亡相关。相比之下，持续活跃的 CD11c 敲入小鼠表现出与效应功能增强相关的中性粒细胞成熟加速，这进一步支持了 CD11c 调节中性粒细胞成熟的观点。此外，组成型活性 CD11c 敲入小鼠可增强细菌根除能力。综上所述，我们发现 CD11c 对于中性粒细胞成熟的调节至关重要，CD11c 的激活可以作为脓毒症治疗的潜在靶标。
CD11c is highly expressed in the intracellular components of developing neutrophils. CD11c regulates the survival and proliferation of developing neutrophils. Sepsis continues to be associated with high morbidity and mortality. Currently, sepsis is managed only conservatively. In sepsis, a substantial number of neutrophils is required, leading to accelerated neutrophil production. Immature neutrophils are released into the circulation to meet a demand, despite their less effective functioning in microbial eradication. Although an intervention to provide more mature neutrophils may serve as a potential sepsis treatment, the mechanism of neutrophil differentiation and maturation remains poorly understood. We discovered that CD11c, traditionally known as a dendritic cell marker, was expressed in neutrophils and regulated neutrophil maturation and effector functions. In the absence of CD11c, neutrophil maturation was impaired in the bone marrow, concomitant with a significant increase in the proliferation and apoptosis of preneutrophils, associated with less effector functions. Under lipopolysaccharide challenge, inducing an emergent neutrophil production in the bone marrow, CD11c deficiency exaggerated the release of immature neutrophils into the circulation, associated with a significant proliferation and apoptosis of preneutrophils. In contrast, constitutively active CD11c knock-in mice showed accelerated neutrophil maturation associated with enhanced effector functions, which further supports the notion that CD11c regulates neutrophil maturation. Furthermore, the constitutively active CD11c knock-in mice offered enhanced bacterial eradication. Taken together, we discovered that CD11c was critical for the regulation of neutrophil maturation, and CD11c activation could serve as a potential target for sepsis treatment.
登录
查看更多内容
常规树突状细胞在调节中性粒细胞骨髓释放和存活中的核心作用。
DOI：
10.4049/jimmunol.1300237
发表时间：
2014-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jiao J;Dragomir AC;Kocabayoglu P;Rahman AH;Chow A;Hashimoto D;Leboeuf M;Kraus T;Moran T;Carrasco-Avino G;Friedman SL;Merad M;Aloman C
通讯作者：
Aloman C
影响因子：
3.7
作者：
Hatton O;Lambert SL;Krams SM;Martinez OM
通讯作者：
Martinez OM
影响因子：
20.3
作者：
Dunne, JL;Ballantyne, CM;Ley, K
通讯作者：
Ley, K
影响因子：
20.3
作者：
Boettcher, Steffen;Gerosa, Rahel C.;Manz, Markus G.
通讯作者：
Manz, Markus G.
影响因子：
56.3
作者：
Levy, Mitchell M.;Artigas, Antonio;Dellinger, R. Phillip
通讯作者：
Dellinger, R. Phillip