NaTuRe RevIeWS| Nephrology that succinate might contribute to blood pressure regulation by inducing renin release in the juxtaglomerular apparatus. The researchers show that luminal succinate sensing via the succinate receptor SUCNR1 regulates and orchestrates transepithelial succinate transport by inducing the translocation of a scaffolding protein, IRBIT, which interacts with the NaDC1–SLC26A6 complex and inhibits succinate transport by NaDC1.“Our findings suggest that the molecular mechanism of succinate–citrate–oxalate homeostasis that we have delineated protects against kidney stone formation and controls blood pressure,” concludes Ohana.“Succinate and citrate signalling and transport mechanisms should be considered potential therapeutic targets for the treatment of hypertension and urolithiasis.” Ellen F. Carney The mechanisms that regulate the transition between systemic inflammatory response syndrome (SIRS) and the endotoxin tolerance (eT) phase in sepsis are not yet clear. Now, Wilfred Jefferies and colleagues report that the aTP-binding cassette gene ABCF1 controls this transition by regulating innate immune responses in macrophages. The researchers previously conducted a gene expression screen and identified ABCF1 as a potential regulator of immunity and inflammation. In their recent study, they show that aBCF1 is an e2 ubiquitin-conjugating enzyme that regulates macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory m2 phenotype by promoting TlR4 endocytosis and activation of TRIF-dependent signalling. In a murine model of sepsis, aBCF1 haploinsufficiency led to increased expression of pro-inflammatory cytokines, failure to transition from SIRS to the eT phase, renal circulatory failure and increased mortality.“During SIRS, the acute inflammatory response caused by pro-inflammatory cytokines damages the host tissue, which ultimately leads to death,” explains Jefferies.“Histological analysis of the aBCF1-deficient mice in the SIRS phase revealed widespread dilation and congestion of small vessels in the kidneys as well as a sludging effect of red blood cells being compacted together in these vessels. This form of vasculature dilation and congestion on a systemic scale results in a critical drop in blood pressure, which leads to insufficient delivery of blood and oxygen to central organs, including the brain and heart.” The researchers conclude that aBCF1 modulates sepsis mortality by promoting transition to the eR phase, thereby repressing hypotension-induced renal circulatory failure.“as aBCF1 switches off pro-inflammatory pathways, our research may provide a map to explore new treatments for chronic and acute inflammatory diseases as well as autoimmune disorders,” says Jefferies. Ellen F. Carney S e PSIS ABCF1 switches off inflammation in sepsis OR g ANO ge N e SIS growing mouse kidneys in rats Interspecific blastocyst complementation is a potential strategy for growing human kidneys in animal hosts. masumi Hirabayashi and colleagues now provide evidence that this approach is viable by using it to grow mouse kidneys in rats.“The process of interspecific blastocyst complementation includes knocking out a gene responsible for renal development in the host animal, maintaining heterogeneous mutant lines to produce homozygous mutant blastocysts, and injecting these blastocysts with exogenous pluripotent stem cells that generate a kidney in the developmental niche,” explains Hirabayashi. Here, the researchers used CRISPR–Cas9 in rats to knock out Sall1, which encodes a protein that is essential for ureteric bud invasion in kidney development in mice. like Sall1 …