Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury

Abstract

Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy.

Gut microbiota promotes pain chronicity in Myosin1A deficient male mice

“…The up-regulation of these sets of genes occurred concomitantly with the up-regulation of genes involved in the inflammatory response and reminiscent of innate immune cells’ recruitment and/or activation, such as myeloid-lineage cells, including monocyte/macrophages (Mo/MΦ). This set contained the Class II transcriptional Activator Ciita that enhances the transcription of MHC II-encoding genes, the CD11b-encoding gene Itgam , widely expressed on myeloid cells, the Colony Stimulating Factor Receptor 1 Csf1r , the chemokine receptor Cx3cr1 and Cd68 , reminiscent of Mo/MΦ recruitment, survival and activation, the Pathogen Recognition Receptors Clec7a , highly expressed in phagocytic MΦ and in pathogenic microglia 36,37 , including in neuropathic-pain promoting microglia 38 and the DAP-12 encoding gene Tyrobp , also up-regulated in pathogenic microglia and necessary for the induction of neuropathic pain 6,39 .…”

“…The copyright holder for this this version posted February 21, 2023. ; https://doi.org/10.1101/2023.02.21.529352 doi: bioRxiv preprint genes, the CD11b-encoding gene Itgam, widely expressed on myeloid cells, the Colony Stimulating Factor Receptor 1 Csf1r, the chemokine receptor Cx3cr1 and Cd68, reminiscent of Mo/Mrecruitment, survival and activation, the Pathogen Recognition Receptors Clec7a, highly expressed in phagocytic M and in pathogenic microglia 36,37 , including in neuropathicpain promoting microglia 38 and the DAP-12 encoding gene Tyrobp, also up-regulated in pathogenic microglia and necessary for the induction of neuropathic pain 6,39 .…”

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages

“…Arginine metabolism genes Arg1 and Odc1 and FAO genes Fabp7, which were all dominantly expressed in GM, positively correlated with Clec7a which highly expressed in GM ( Figure 6B ; Table S2 ). According to the research conducted by Wang et al., Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compare to Clec7a- population ( 60 ). Once pathogens infiltrate cells, their eradication occurs by the lysosome through a series of gene regulation and protein interaction, such as Lamp1, P62, and LC3 in the autophagy process ( 61 , 62 ).…”