Endothelial progenitor cells (EPCs) contribute to neovascularization and endothelial repair during injury. An increase in the number and function of EPCs in circulation has been noted among patients with cirrhosis.

Natural killer (NK) cells are known to regulate EPCs. Therefore, in the present study, Sehgal and colleagues explored the link between the two in 50 patients with alcoholic cirrhosis (AC) and 18 with severe alcoholic hepatitis (SAH).They were compared with 15 nonalcoholic cirrhosis patients and 30 healthy controls (HC).

SAH patients were reported to have higher regulated on activation, normal T cell expressed and secreted (RANTES), vascular endothelial growth factor (VEGF), IL-1β, and IL-6 growth factors as well as proinflammatory cytokines, in comparison with AC patients and HCs. Distinct populations of CD31+ CD34+ EPCs with low and high expression of CD45 were found to be significantly lower in SAH patients compared to HCs and AC patients. Furthermore, SAH patients had increased functional capacity of EPCs, including colony formation and LDL uptake.

There was a reduction in NK cells in SAH patients compared with AC patients, but with higher granzyme ability. EPC-NK cell interaction assays among SAH patients revealed that NK cells led to lysis of the EPCs in both contact-dependent and contact-independent assays. CX3CR1 expression was significantly higher on NK cells. Its cognate receptor, fractalkine (FKN), was shown to be increased on EPCs in SAH patients when compared with HCs.

The study thus revealed that in SAH patients, NK cells induce lysis of EPCs through the CX3CR1/FKN axis which could be one of the major events that have a role in disease severity and proinflammatory responses in SAH.

Source: Sehgal R, Kaur S, Shasthry SM, et al. Natural Killer Cells Contribute to Pathogenesis of Severe Alcoholic Hepatitis by Inducing Lysis of Endothelial Progenitor Cells. Alcohol Clin Exp Res. 2020 Jan;44(1):78-86.