Genotoxic stress signalling as a driver of macrophage diversity.

IF 4.1 Q2 CELL BIOLOGY
Cell Stress Pub Date : 2022-02-14 eCollection Date: 2022-03-01 DOI:10.15698/cst2022.03.265
Ana Kasapi, Antigoni Triantafyllopoulou
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引用次数: 4

Abstract

Tissue macrophages arise from yolk sac, fetal liver and hematopoietic progenitors and adopt diverse transcriptional programs and phenotypes, instructed by their microenvironment. In chronic inflammation, such as in chronic infections, autoimmunity, or cancer, tissue microenvironments change dramatically thus imprinting new programs on tissue macrophages. While stress is a known driver of carcinogenesis in epithelial cells, emerging evidence suggests that macrophage responses to genotoxic stress are embedded in their 'physiologic' immune and tissue healing programs and in most cases do not lead to myeloid malignancies. The role of genotoxic stress as an instructor of macrophage-mediated immune defense and tissue remodeling is only beginning to be understood. Here, we review the evidence showing that genotoxic stress, which macrophages and their precursors face upon encountering inflammatory and/or growth signals, instructs their transcriptional programs, by activating non-canonical, cell-type specific DNA Damage Response (DDR)-driven signaling pathways. We propose that immune-cell specific, DDR-instructed programs are crucial for tissue homeostasis as well as for the maintenance and resolution of inflammatory responses in infection, cancer, autoinflammatory and autoimmune microenvironments.

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基因毒性应激信号作为巨噬细胞多样性的驱动因素。
组织巨噬细胞起源于卵黄囊、胎肝和造血祖细胞,受微环境的影响,具有多种转录程序和表型。在慢性炎症中,如慢性感染、自身免疫或癌症,组织微环境发生巨大变化,从而在组织巨噬细胞上印记新的程序。虽然压力是上皮细胞致癌的一个已知驱动因素,但新出现的证据表明,巨噬细胞对基因毒性压力的反应嵌入其“生理性”免疫和组织愈合程序中,在大多数情况下不会导致髓系恶性肿瘤。基因毒性应激作为巨噬细胞介导的免疫防御和组织重塑的指导者的作用才刚刚开始被理解。在这里,我们回顾了巨噬细胞及其前体在遇到炎症和/或生长信号时所面临的基因毒性应激,通过激活非规范的、细胞类型特异性DNA损伤反应(DDR)驱动的信号通路来指导它们的转录程序。我们认为免疫细胞特异性、ddr指示的程序对于组织稳态以及在感染、癌症、自身炎症和自身免疫微环境中炎症反应的维持和解决至关重要。
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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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