Intestinal microvascular changes associated with the induction and perpetuation of chronic gut inflammation

Abstract

Adoptive transfer of naïve CD4+ T‐cells into lymphopenic mice induces chronic small and large bowel inflammation similar to Crohn's disease. Although much is now known regarding the immunopathology in this model of inflammatory bowel disease, virtually nothing is known about the microvascular hemodynamic changes in the induction and perpetuation of chronic gut inflammation. In this study, CD4+CD45RBhigh T‐cells obtained from healthy C57BL6 donors were transferred into lymphopenic recombinase activating gene‐1 deficient (RAG ko) mice, and in the following weeks, intravital microscopy was used to examine the ileum and proximal colon. Measurements included arteriolar diameters and the velocity of labeled platelets (indicator of blood velocity), with the results compared to unreconstituted RAG ko controls. In < 1 wk following reconstitution, velocity and wall shear rate of the arterioles decreased by > 50% compared to controls, with this decrease also observed at 4‐5 and 7‐9 weeks post‐reconstitution. At 7‐9 weeks, arteriolar diameters were found to be ~15% larger than in controls, but despite this dilation, flow rates in the individual vessels were decreased by ~30%. Whether the overall intestinal flow rate is decreased in this model may be dependent on the reported angiogenesis, which could explain the lower individual vessel flows despite the late vasodilation. Supported by Projects 1 & 2 of NIH P01DK043785.