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Original Research Full Report: Basic and Translational—Alimentary Tract| Volume 160, ISSUE 5, P1679-1693, April 01, 2021

Single-Cell Transcriptional Survey of Ileal-Anal Pouch Immune Cells From Ulcerative Colitis Patients

Published:December 21, 2020DOI:https://doi.org/10.1053/j.gastro.2020.12.030

      Background & Aims

      Restorative proctocolectomy with ileal pouch–anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized during pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing (scRNA-seq).

      Methods

      We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n = 15) and without an ileal pouch–anal anastomosis (n = 11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches.

      Results

      In addition to tissue-specific signatures, we identified a population of IL1B/LYZ+ myeloid cells and FOXP3/BATF+ T cells that distinguish inflamed tissues, which we further validated in other scRNA-seq datasets from patients with inflammatory bowel disease (IBD). Cell-type–specific transcriptional markers obtained from scRNA-seq was used to infer representation from bulk RNA sequencing datasets, which further implicated myeloid cells expressing IL1B and S100A8/A9 calprotectin as interacting with stromal cells, and Bacteroidales and Clostridiales bacterial taxa. We found that nonresponsiveness to anti-integrin biologic therapies in patients with ulcerative colitis was associated with the signature of IL1B+/LYZ+ myeloid cells in a subset of patients.

      Conclusions

      Features of intestinal inflammation during pouchitis and ulcerative colitis are similar, which may have clinical implications for the management of pouchitis. scRNA-seq enables meta-analysis of multiple studies, which may facilitate the identification of biomarkers to personalize therapy for patients with IBD.
      The processed single cell count tables are provided in Gene Expression Omnibus; GSE162335. Raw sequence data are not public and are protected by controlled-access for patient privacy.

      Keywords

      Abbreviations used in this paper:

      CD (Crohn’s disease), DC (dendritic cell), DE (differential expression), FAP (familial adenomatous polyposis), FDA (Food and Drug Administration), IBD (inflammatory bowel disease), IL (interleukin), IPAA (ileal pouch–anal anastomosis), ISCORE (composite inflammation score), PCA (principal component analysis), PDAI (pouchitis disease activity index), scRNA-seq (single-cell RNA sequencing), TNF (tumor necrosis factor), UC (ulcerative colitis)
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