Open AccessJournal Article
Irf5 promotes inflammatory macrophage polarization and th1/th17 response
Thomas Krausgruber,Katrina Blazek,Timothy Smallie,Helen Lockstone,Natasha Sahgal,Saba Alzabin,Tracy Hussell,Marc Feldmann,Irina A. Udalova +8 more
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TLDR
The authors showed that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization, leading to a potent T helper type 1 (TH1)-TH17 response.Abstract:
Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (TH1)-TH17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor.read more
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Journal ArticleDOI
Macrophage plasticity and polarization: in vivo veritas
Antonio Sica,Alberto Mantovani +1 more
TL;DR: The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for Macrophage-centered diagnostic and therapeutic strategies.
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Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines
Peter J. Murray,Judith E. Allen,Subhra K. Biswas,Edward A. Fisher,Derek W. Gilroy,Sergij Goerdt,Siamon Gordon,John A. Hamilton,Lionel B. Ivashkiv,Toby Lawrence,Massimo Locati,Alberto Mantovani,Fernando O. Martinez,Jean-Louis Mege,David M. Mosser,Gioacchino Natoli,Jeroen P. J. Saeij,Joachim L. Schultze,Kari Ann Shirey,Antonio Sica,Jill Suttles,Irina A. Udalova,Jo A. Van Ginderachter,Stefanie N. Vogel,Thomas A. Wynn +24 more
TL;DR: A set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation are described with the goal of unifying experimental standards for diverse experimental scenarios.
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Protective and pathogenic functions of macrophage subsets
Peter J. Murray,Thomas A. Wynn +1 more
TL;DR: The four stages of orderly inflammation mediated by macrophages are discussed: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis.
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The M1 and M2 paradigm of macrophage activation: time for reassessment.
TL;DR: How cytokines and pathogen signals influence macrophages' functional phenotypes and the evidence for M1 and M2 functions is assessed and a paradigm initially based on the role of a restricted set of selected ligands in the immune response is revisited.
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Macrophage biology in development, homeostasis and disease
TL;DR: This Review discusses how macrophage regulate normal physiology and development, and provides several examples of their pathophysiological roles in disease, and defines the ‘hallmarks’ of macrophages according to the states that they adopt during the performance of their various roles.
References
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Alternative activation of macrophages
TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Journal ArticleDOI
Monocyte and macrophage heterogeneity
Siamon Gordon,Philip R. Taylor +1 more
TL;DR: Recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues.
Journal ArticleDOI
Macrophage plasticity and polarization: in vivo veritas
Antonio Sica,Alberto Mantovani +1 more
TL;DR: The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for Macrophage-centered diagnostic and therapeutic strategies.
Journal ArticleDOI
IL-17 and Th17 Cells.
TL;DR: The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation and now appreciate the importance of Th 17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.
Journal ArticleDOI
Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines
Peter J. Murray,Judith E. Allen,Subhra K. Biswas,Edward A. Fisher,Derek W. Gilroy,Sergij Goerdt,Siamon Gordon,John A. Hamilton,Lionel B. Ivashkiv,Toby Lawrence,Massimo Locati,Alberto Mantovani,Fernando O. Martinez,Jean-Louis Mege,David M. Mosser,Gioacchino Natoli,Jeroen P. J. Saeij,Joachim L. Schultze,Kari Ann Shirey,Antonio Sica,Jill Suttles,Irina A. Udalova,Jo A. Van Ginderachter,Stefanie N. Vogel,Thomas A. Wynn +24 more
TL;DR: A set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation are described with the goal of unifying experimental standards for diverse experimental scenarios.