2017 Cardiovascular Research Day Abstract Book

77
The Role of ApoC-III in the immune system
Alison Kohan, PhD 1 • Cayla Rodia 1
1Nutritional Sciences, University of Connecticut
Faculty
While we know that CD4+CD25+Foxp3+ regulatory T cells (Tregs) are a powerful tool in the
resolution of gut inflammation, and that their secretion of IL-10 is critical to inflammatory bowel
disease (IBD) remission, there is a major gap in identifying mechanisms for increasing Tregs in the
intestine. Recently, we have found that intestinal Tregs and plasma IL-10 are dramatically
increased in mice overexpressing human apoC-III. These intestinal Tregs significantly protect apoC-
III transgenic mice mice from experimental colitis, including weight loss, diarrhea, and TNF-α
secretion. While apoC-III overexpression is protective, loss of apoC-III in apoC-III-/- mice severely
impacts colitis sensitivity; more than 50% of apoC-III-/- mice die in response to dextran sodium
sulfate (DSS)-colitis induction, compared to wild-type controls that all survive. Supporting our
studies in these mouse models are human studies which show that both plasma and ileal apoC-III
levels are reduced in patients during active IBD flare-ups. We have now determined that apoC-III
acts specifically on Tregs and CD103+dendritic cells in the intestine and mesenteric lymph nodes,
and that treatment of Tregs ex vivo with apoC-III-containing lipoproteins inhibits their ability to
take up extracellular fatty acids. This inhibitory role of apoC-III on lipid uptake is well known, but
this is the first time this role has been described in Tregs, thus defining a new and biologically
important function of this apolipoprotein in the immune system. We hypothesize that a critical
function of apoC-III is to regulate lipid uptake and metabolism in intestinal Tregs, which results in
increased tolerogenicity in the gut.
93