Molecular and epigenetic basis of macrophage polarized activation.

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156

作者：

C Porta，E Riboldi，A Ippolito，A Sica

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摘要：

Macrophages are unique cells for origin, heterogeneity and plasticity. At steady state most of macrophages are derived from fetal sources and maintained in adulthood through self-renewing. Despite sharing common progenitors, a remarkable heterogeneity characterized tissue–resident macrophages indicating that local signals educate them to express organ-specific functions. Macrophages are extremely plastic: chromatin landscape and transcriptional programs can be dynamically re-shaped in response to microenvironmental changes. Owing to their ductility, macrophages are crucial orchestrators of both initiation and resolution of immune responses and key supporters of tissue development and functions in homeostatic and pathological conditions. Herein, we describe current understanding of heterogeneity and plasticity of macrophages using the M1–M2 dichotomy as operationally useful simplification of polarized activation. We focused on the complex network of signaling cascades, metabolic pathways, transcription factors, and epigenetic changes that control macrophage activation. In particular, this network was addressed in sepsis, as a paradigm of a pathological condition determining dynamic macrophage reprogramming.

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关键词：

Macrophage Activation Plasticity Metabolism Epigenetic Gene expression HSCs, hematopoietic stem cells EMPs, erythro-myeloid progenitors LCs, Langerhans cells BM, bone marrow TRAP, Tartrate-resistant acid phosphatase RP, red pulp MZ, marginal zone AMs, alveolar macrophages IMs, interstitial macrophages PIMs, pulmonary intravascular macrophages LPS, Lipopolysaccharide SOCS, suppressor of cytokine signaling PGE2, prostaglandin E2 STAT, Signal Transducer and Activator of Transcription DMs, dermal macrophages LDTFs, lineage-determining transcription factors GATA6, GATA-binding protein 6 GM-CSF, Granulocyte-macrophage colony-stimulating factor PPARγ, peroxisome proliferator-activated receptor-γ RANK, Receptor activator of nuclear factor kappa-B LXRα, transcription factors liver X receptor α iNOS, inducible nitric oxide synthase NO, nitric oxide ROS, reactive oxygen species IRF, Interferon Regulatory Factor PFK2, 6-phosphofructose-2-kinase/fructose-2,6-bisphosphatase CARKL, carbohydrate kinase-like protein IDH, isoc