Complosome - the intracellular complement system.
Complosome - the intracellular complement system.
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DOI：
10.1038/s41581-023-00704-1
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发表时间：
2023-07
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影响因子：
--
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中科院分区：
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--
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补体系统是公认的宿主防御感染和有害的自身衍生抗原的支柱。补体在传统上被称为血清有效系统，肝脏表达和分泌大多数补体成分，这些成分参与血液传播病原体的检测并驱动炎症反应以安全地消除微生物或抗原威胁。然而，正常补体功能的扰动可导致严重疾病，并且由于目前尚未完全理解的原因，肾脏特别容易受到补体活性失调的影响。对补体生物学的新见解已经确定了细胞自主和细胞内活性补体-补体体-作为正常细胞生理学的意想不到的中央协调器。例如，在先天性和适应性免疫细胞中，以及在非免疫细胞（如成纤维细胞和内皮细胞和上皮细胞）中，所述复合体控制线粒体活性、糖酵解、氧化磷酸化、细胞存活和基因调节。这些未预料到的补体对基本细胞生理途径的贡献使其成为控制细胞稳态和效应器反应的新型和中心参与者。这一发现以及越来越多的人类疾病涉及补体扰动的认识，重新引起了人们对补体系统及其治疗靶向的兴趣。在这里，我们总结了目前关于健康细胞和组织中的补体的知识，强调了失调的补体活动对人类疾病的贡献，并讨论了潜在的治疗意义。具有细胞内活性的补体蛋白和受体--补体体--已经成为生理过程的重要调节剂。在这篇综述中，作者研究了多种细胞和组织中补体活性的证据，以及它们对人类疾病和治疗潜力的贡献。补体功能是区室化的，并且在系统、局部地在细胞外空间中以及在亚细胞区室和细胞器内的细胞内起作用。细胞内补体-补体体-作为基本细胞生理过程（包括线粒体呼吸、糖酵解、自噬和基因转录）的新型中央调节器发挥非经典作用。补体体在免疫和非免疫细胞和组织中起作用，在那里它控制正常细胞更新、对感染性和非感染性刺激的反应以及恢复稳态。复杂体活性的扰动导致人类疾病，包括感染和感染相关的病理状况、关节炎疾病、动脉粥样硬化、癌症和肾病。靶向补体体，可能与细胞外活性补体组合，可能在补体介导的病理状况中是治疗有益的。
The complement system is a recognized pillar of host defence against infection and noxious self-derived antigens. Complement is traditionally known as a serum-effective system, whereby the liver expresses and secretes most complement components, which participate in the detection of bloodborne pathogens and drive an inflammatory reaction to safely remove the microbial or antigenic threat. However, perturbations in normal complement function can cause severe disease and, for reasons that are currently not fully understood, the kidney is particularly vulnerable to dysregulated complement activity. Novel insights into complement biology have identified cell-autonomous and intracellularly active complement — the complosome — as an unexpected central orchestrator of normal cell physiology. For example, the complosome controls mitochondrial activity, glycolysis, oxidative phosphorylation, cell survival and gene regulation in innate and adaptive immune cells, and in non-immune cells, such as fibroblasts and endothelial and epithelial cells. These unanticipated complosome contributions to basic cell physiological pathways make it a novel and central player in the control of cell homeostasis and effector responses. This discovery, together with the realization that an increasing number of human diseases involve complement perturbations, has renewed interest in the complement system and its therapeutic targeting. Here, we summarize the current knowledge about the complosome across healthy cells and tissues, highlight contributions from dysregulated complosome activities to human disease and discuss potential therapeutic implications. Complement proteins and receptors with intracellular activity — the complosome — have emerged as important regulators of physiological processes. In this Review, the authors examine evidence of complosome activity across a variety of cells and tissues, as well as their contributions to human disease and therapeutic potential. Complement function is compartmentalized and operates systemically, locally in the extracellular space, and intracellularly within sub-cellular compartments and organelles. Intracellular complement — the complosome — serves non-classical roles as a novel central regulator of basic cell physiological processes including mitochondrial respiration, glycolysis, autophagy and gene transcription. The complosome functions across immune and non-immune cells and tissues where it controls normal cell turnover, the responses to infectious and non-infectious stimuli and the return to homeostasis. Perturbations in complosome activities contribute to human disease, including infections and infection-related pathological conditions, arthritic disease, atherosclerosis, cancer and kidney disease. Targeting the complosome, possibly in combination with the extracellularly active complement, might be therapeutically beneficial in complement-mediated pathological conditions.
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影响因子：
2.8
作者：
Ni Choileain, Siobhan;Astier, Anne L.
通讯作者：
Astier, Anne L.
影响因子：
16.6
作者：
Arbore G;West EE;Rahman J;Le Friec G;Niyonzima N;Pirooznia M;Tunc I;Pavlidis P;Powell N;Li Y;Liu P;Servais A;Couzi L;Fremeaux-Bacchi V;Placais L;Ferraro A;Walsh PR;Kavanagh D;Afzali B;Lavender P;Lachmann HJ;Kemper C
通讯作者：
Kemper C
影响因子：
--
作者：
Bosmann, Markus;Ward, Peter A.
通讯作者：
Ward, Peter A.
DOI：
10.4049/jimmunol.2101170
发表时间：
2022-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL