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.
Highlights
Macrophages (Mφs) are a group of circulating/resident mononuclear cells involved in tissue homeostasis, characterized by a phenotypic heterogeneity and a profound cell plasticity
dendritic cells (DCs) play a main role as antigen presenting cells (APCs), acting as a red thread between innate and adaptive immunity, internalizing and processing antigens, and presenting peptides bound to the major histocompatibility complexes I and II to T cells [3,13]; overall they shape the local immunity for peripheral tolerance [14]
In a recent manuscript, Wei et al [113], demonstrated in a rodent model of acute antibody mediated rejection (AMR) that MHC I donor-specific alloantibodies (DSA) upregulated genes related to monocyte transmigration promoting monocyte differentiation into CD68+CD206+CD163+Mφ, enforcing the concept that infiltrating Mφ may contribute to vascular injury during AMR
Summary
Macrophages (Mφs) are a group of circulating/resident mononuclear cells involved in tissue homeostasis, characterized by a phenotypic heterogeneity and a profound cell plasticity. Data on the composition of the human renal phagocytic system in normal conditions are extremely sparse and essentially rely on either the analysis of “normal” tissue areas distal to a cancerous lesion obtained from routine nephrectomies [7], or on biopsy areas without lesions, derived from patients with non-identifiable diseases. Based on those studies, the normal human kidney mainly possesses a DC system composed of interstitial DCs and DC precursors. Two preliminary sections, dedicated to the analysis of macrophage heterogeneity and their phenotypic specificity in the renal compartments, were included to facilitate understanding of the role of macrophage in glomerulonephritis and renal transplantation
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