Postdoctoral researcher Washington University in St.Louis Saint Louis, Missouri, United States
Introduction/Rationale: The superior mesenteric and portal venous tracts transport small intestinal venous blood rich in nutrients and metabolites to the liver, serving as a critical interface in the gut–liver axis. Characterizing transport in the enterohepatic circulation is important, yet this process remains incompletely understood.
Methods: Leukocyte counts were quantified by flow cytometry from multiple venous depots in mice. A 2% cholestyramine diet was used to inhibit ileal bile acid uptake. The impact of Th17 immunity was evaluated by comparing Jackson C57BL/6 and SFB-colonized mice, performing fecal transfers from SFB-replete donors, applying IL-17A neutralization, and stimulating CD3ε during fasting.
Results: While characterizing this circulation, we found that portal venous leukocyte counts—but not erythrocyte counts—were at least 2-fold higher than in other venous depots in the mouse. Overnight fasting normalized portal leukocyte numbers relative to other sites, suggesting that nutrient intake modulated this outcome. Because bile acid levels fall during fasting, we tested whether enterohepatic circulation contributes to this effect. Inhibition of bile acid uptake with a 2% cholestyramine diet reduced portal leukocytes to near-fasting levels. However, fasting failed to normalize elevated leukocyte counts in SFB-colonized mice with increased IL17a transcripts. Transfer of SFB-replete feces prevented fasting-induced leukocyte reduction, whereas IL-17A neutralization restored it. CD3ε stimulation during fasting increased portal leukocytes, indicating that Th17 activity counteracts fasting-induced suppression.
Conclusion: The underlying mechanism explaining how bile acid recirculation or IL-17 signaling leads to accumulated leukocytes the venous outflow from the small intestine remains unclear. We are currently testing whether these signals activate the venous endothelial cells to support enhanced leukocyte rolling/sticking without supporting diapedesis, a mechanism that could explain observed immune enrichment.
