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      Glomerular Macrophages in Human Auto- and Allo-Immune Nephritis

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          Abstract

          Macrophages are involved in tissue homeostasis. They participate in inflammatory episodes and are involved in tissue repair. Macrophages are characterized by a phenotypic heterogeneity and a profound cell plasticity. In the kidney, and more particularly within glomeruli, macrophages are thought to play a maintenance role that is potentially critical for preserving a normal glomerular structure. Literature on the glomerular macrophage role in human crescentic glomerulonephritis and renal transplantation rejection with glomerulitis, is sparse. Evidence from preclinical models indicates that macrophages profoundly modulate disease progression, both in terms of number—where depletion has resulted in a reduced glomerular lesion—and sub-phenotype—M1 being more profoundly detrimental than M2. This evidence is corroborated by better outcomes in patients with a lower number of glomerular macrophages. However, due to the very limited biopsy sample size, the type and role of macrophage subpopulations involved in human proliferative lesions is more difficult to precisely define and synthesize. Therefore, specific biomarkers of macrophage activation may enhance our ability to assess their role, potentially enabling improved monitoring of drug activity and ultimately allowing the development of novel therapeutic strategies to target these elusive cellular players.

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          Most cited references113

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          Exploring the full spectrum of macrophage activation.

          Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
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            The chemokine system in diverse forms of macrophage activation and polarization.

            Plasticity and functional polarization are hallmarks of the mononuclear phagocyte system. Here we review emerging key properties of different forms of macrophage activation and polarization (M1, M2a, M2b, M2c), which represent extremes of a continuum. In particular, recent evidence suggests that differential modulation of the chemokine system integrates polarized macrophages in pathways of resistance to, or promotion of, microbial pathogens and tumors, or immunoregulation, tissue repair and remodeling.
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              Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms

              The alternatively activated or M2 macrophages are immune cells with high phenotypic heterogeneity and are governing functions at the interface of immunity, tissue homeostasis, metabolism, and endocrine signaling. Today the M2 macrophages are identified based on the expression pattern of a set of M2 markers. These markers are transmembrane glycoproteins, scavenger receptors, enzymes, growth factors, hormones, cytokines, and cytokine receptors with diverse and often yet unexplored functions. This review discusses whether these M2 markers can be reliably used to identify M2 macrophages and define their functional subdivisions. Also, it provides an update on the novel signals of the tissue environment and the neuroendocrine system which shape the M2 activation. The possible evolutionary roots of the M2 macrophage functions are also discussed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                09 March 2021
                March 2021
                : 10
                : 3
                : 603
                Affiliations
                [1 ]Department of Pathology, University Hospital of Geneva, 1205 Geneva, Switzerland; Solange.Moll@ 123456hcuge.ch
                [2 ]Nephrology, Dialysis and Transplantation Unit, Giannina Gaslini Scientific Institute for Research, Hospitalization and Healthcare, 16147 Genoa, Italy; andreaangeletti@ 123456gaslini.org (A.A.); GMarcoGhiggeri@ 123456gaslini.org (G.M.G.)
                [3 ]Institute of Pharmaceutical Sciences of Western Switzerland, School of Pharmaceutical Sciences, University of Geneva, 1205 Geneva, Switzerland; Leonardo.Scapozza@ 123456unige.ch
                [4 ]Institute for Research in Biomedicine (IRB), Università della Svizzera Italiana (USI), 6900 Lugano, Switzerland; andrea.cavalli@ 123456irb.usi.ch
                [5 ]Galapagos NV, 4051 Basel, Switzerland
                Author notes
                [* ]Correspondence: marco.prunotto@ 123456unige.ch or marco.prunotto@ 123456glpg.com ; Tel.: +41-79-578-4276 or +41-22-379-4255
                Author information
                https://orcid.org/0000-0002-6121-5326
                https://orcid.org/0000-0003-1079-648X
                https://orcid.org/0000-0002-0203-0129
                Article
                cells-10-00603
                10.3390/cells10030603
                7998925
                76a043d4-0406-4f33-bc92-195560ce81c7
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 December 2020
                : 04 March 2021
                Categories
                Review

                glomerulonephritis,macrophages,immune nephritis
                glomerulonephritis, macrophages, immune nephritis

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