Macrophage-Specific MCPIP1/Regnase-1 Attenuates Kidney Ischemia-Reperfusion Injury by Shaping the Local Inflammatory Response and Tissue Regeneration

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-01, Vol.11 (3), p.397
• Main Authors: Ribeiro, Andrea, Dobosz, Ewelina, Krill, Moritz, Köhler, Paulina, Wadowska, Marta, Steiger, Stefanie, Schmaderer, Christoph, Koziel, Joanna, Lech, Maciej
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - metabolism; Animals; Antibodies; Cell activation; Creatinine; Fibrosis; Granulocytes; Homeostasis; Immune response; Immune system; Inflammation; Inflammation - metabolism; Interferon regulatory factor 4; Ischemia; ischemia-reperfusion; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Laboratories; Leukocytes (neutrophilic); Macrophages; Macrophages - enzymology; MCPIP1; Mice; Monocyte chemoattractant protein; Monocyte Chemoattractant Proteins - metabolism; Monocytes; Neutrophils; Pathophysiology; Phenotypes; Proteins; Reperfusion; Reperfusion Injury - metabolism; Ribonucleases - genetics; Transgenic mice; Urine
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11030397

Sterile inflammation either resolves the initial insult or leads to tissue damage. Kidney ischemia/reperfusion injury (IRI) is associated with neutrophilic infiltration, enhanced production of inflammatory mediators, accumulation of necrotic cells and tissue remodeling. Macrophage-dependent microenvironmental changes orchestrate many features of the immune response and tissue regeneration. The activation status of macrophages is influenced by extracellular signals, the duration and intensity of the stimulation, as well as various regulatory molecules. The role of macrophage-derived monocyte chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, in kidney ischemia-reperfusion injury (IRI) and recovery from sterile inflammation remains unresolved. In this study, we showed that macrophage-specific deletion significantly affects the kidney phenotype. Macrophage-specific transgenic mice displayed enhanced inflammation and loss of the tubular compartment upon IRI. We showed that MCPIP1 modulates sterile inflammation by negative regulation of expression and accumulation of IRF4+ cells in the tissue and, consequently, suppresses the post-ischemic kidney immune response. Thus, we identified MCPIP1 as an important molecular sentinel of immune homeostasis in experimental acute kidney injury (AKI) and renal fibrosis.