MUCOSAL IMMUNE SIGNATURES OF PERIANAL FISTULIZING CROHN’S DISEASE BY MASS CYTOMETRY

Abstract BACKGROUNDS Perianal fistulas occur in ~30-40% of patients associated with high morbidity and an impaired quality life. The management perianal fistulizing CD is a major clinical challenge, where its underlying etiology poorly understood. METHODS We recruited history of: 1) fistulas; 2) without involvement; 3) idiopathic fistulas. Biopsies were taken from the fistula tracts, external opening fistulas, rectal mucosa during examination under anesthesia or colonoscopy. Isolated mucosal immune cells analyzed using mass cytometry. Data was viSNE for dimensionality reduction. RESULTS have revealed previously unknown landscapes Key cell populations significant difference frequencies are summarize Table 1 (data not shown due to limited space): CD45RO+ T including Tregs elevated compared those which consistent prior histological study. expression co-inhibitory receptor TIGIT co-stimulatory CD226 increased although their function IBD especially remains unclear. Th17 tracts IL-17-producing CD8 (Tc17) rectum, highlight importance IL-17 signaling CD. show CD39 decreased CD127 (IL-7Ra) both CD4 cells. markers exhaustion, may control pathogenesis by regulating cytokine production. 4) Total B In contrast, regulatory (Bregs), immunomodulatory gut, dramatically diminished 5) Besides adaptive cells, CD3-CD19- innate lymphoid (ILCs), macrophages, NK also skewed Fistula shown), rectum all CD172+TREM1+ found promote chronic inflammation luminal CONCLUSIONS responses demonstrate unique features that present (summarized Figure 1). This indicates represents identity distinct intestine. Importantly, altered exhaustion (CD39 CD127) pathogenic macrophages three locations (fistula opening, rectum) CD, suggesting roles become novel therapeutic targets.