Presenting Author: Sydney Crotts
, PhD Candidate at Mayo Clin., Minnesota
Abstract:
Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) affects between 1-3 million people in the United States and costs an estimated $11-28 billion in US national healthcare costs. IBD patients present with symptoms including diarrhea, rectal bleeding, and fatigue. ST8Sia6 is a sialic acid transferase that adds terminal a2,8 disialic acids to cell surface glycoproteins, and a SNP in ST8Sia6 is associated with Crohn’s Disease in humans. We have found that ST8Sia6 knockout (KO) and ST8Sia6 heterozygous (het) mice exhibit increased spontaneous small bowel (SB) lamina propria immune infiltration and an increased proportion of T-bet+ and T-bet+RORγT+ CD4 effector cells, resulting in a 30-180-fold increase in the number of these polarized CD4 T cells. Additionally, the KO mice exhibit increased inflammatory cytokine production, decreased IgA class switching of SB plasma cells, and alterations of the SB innate lymphoid cells, all indicative of gut inflammation. Both ST8Sia6 KO and het mice exhibit increased weight loss and decreased survival when challenged with dextran sodium sulfate (DSS)-induced colitis. These data demonstrate a role for ST8Sia6 in regulating gut immune homeostasis, and elucidating this role will aid in developing a mechanistic understanding of IBD pathogenesis to potentially design immunotherapies for the disease.
A novel role for ST8Sia6 in restraining inflammatory bowel disease
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1