A171 INTESTINAL INTERFERON-LAMBDA RECEPTOR 1 EXPRESSION AND RESPONSES ARE SIGNIFICANTLY DECREASED IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS

Abstract Background While interferon-lambdas (IFN-λs) were initially discovered for their role in antiviral immunity at mucosal barriers such as the lung and gut, there are many unanswered questions how IFN-λs uniquely dampen inflammatory immune responses. In mouse colitis models, shown to play a significant promoting epithelial barrier integrity healing. Microbes present gut naturally induce IFN-λs, but chronic inflammation, patients with bowel diseases (IBD), affects IFN-λ biology has not been well studied, especially humans. Purpose Here, we tested hypothesis that children active, more severe IBD would lower intestinal IFN-λR levels responses which could contribute pathology through exacerbated decreased healing impaired function. Method We screened 14 novel antibodies find optimal clone accurately stains unique receptor subunit (IFN-λR1) protein human tissue IFN-λR1 quantified by immunohistochemistry flow cytometry biopsy samples from without IBD, Crohn’s disease, or ulcerative (n=35 total). Fresh patient biopsies (ascending colon terminal ileum) also treated media +/- 24hrs using our ex vivo assay changes gene expression RT-qPCR. Intestinal washes collected microbes profiled shotgun metagenomics. Result(s) identified 2 new stained cell lines cells known express (gut B cells). found (IFN-λR) significantly reduced within pediatric tissue, even non-inflamed sites (p<0.01, 30-50% reduction) this was pronounced when comparing moderate/severe disease compared no activity. This led responsiveness non-IBD investigating IFN-stimulated (p<0.05, up 7-fold reduction). Paired microbe analyses specific species correlated expression. Conclusion(s) Together, findings demonstrate may be less able critical IFN-λ-mediated antimicrobial protective anti-inflammatory pathways. work supports goal restore promote therapeutic strategy IBD. Please acknowledge all funding agencies checking applicable boxes below Other indicate your source of funding; Children's Hospital Research Institute Manitoba Disclosure Interest None Declared