A subset of Kupffer cells regulates metabolism through the expression of CD36

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

“…This analysis identified one subset of KCs. However, 2 subpopulations termed KC1 and KC2 have recently been described ( Blériot et al., 2021 ; Simone et al., 2021 ). As our CITE-seq analysis identified that the markers used to identify KC2s, namely CD206 and ESAM, are largely expressed by liver sinusoidal endothelial cells (LSECs) ( Figure S2 E), we next sought to determine if we had previously removed any potential KC2s in our initial QC steps as LSEC-KC doublets.…”

“…In this UMAP, we found multiple subpopulations including 3 populations of KCs and 2 populations of B cells ( Figure S2 F). To determine if any of these populations could be KC2s, we harnessed the power of CITE-seq to recreate the gating strategy recently proposed to identify KC2s ( Blériot et al., 2021 ). Converting the CITE-seq data into an FCS file and analyzing this in FlowJo identified 2 of the KC populations to be KC2s expressing CD206 and ESAM, and these cells were present in a similar ratio among KCs as reported by Blériot et al.…”

Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

“…In parallel to the present study, we have used high-dimensional single-cell sequencing, mass cytometry, and flow cytometry, coupled with in vivo fate-mapping models to perform an in-depth characterization of KC2 at steady state (Bleriot et al, 2021, this issue of Immunity). These analyses have revealed a specific metabolic role for KC2 in regulating glucose homeostasis and oxidative stress (Bleriot et al, 2021). Future studies should be directed at identifying the signals required for KC2 development and maintenance and explore the potential role of these cells in other diseases affecting the liver.…”

The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

“…However, Blériot et al recently described a minor CD206 hi ESAM + KC subset that is predominantly wired with metabolic functions and expresses surface markers previously thought to be exclusive for liver sinusoidal endothelial cells. These KCs present with a different transcriptional profile compared to their immunomodulatory counterparts, but express the KC core signature and are embryonic derived [ 56 ]. Murine KCs primarily originate from fetal yolk-sac-derived progenitors and self-renew via M-CSF-dependent proliferation [ 37 ].…”

“…The functional heterogeneity of the KC pool during NAFLD was very recently reported to be even more complex than previously reported. Blériot et al described a metabolically wired KC subset that prevents HFD-induced weight gain and oxidative stress when conditionally depleted [ 56 ]. Future kinetic and conditional depletion studies of each of these described KC subsets in a variety of NAFLD models are needed to describe their dynamics and more clearly define the roles of KC subsets and (pre)MoKCs during NAFLD initiation and progression.…”