RT Journal Article
SR Electronic
T1 Transcriptional Atlas of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis Patients
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.31.231308
DO 10.1101/2020.07.31.231308
A1 Joseph C. Devlin
A1 Jordan Axelrad
A1 Ashley M. Hine
A1 Shannon Chang
A1 Suparna Sarkar
A1 Jian-Da Lin
A1 Kelly V. Ruggles
A1 David Hudesman
A1 Ken Cadwell
A1 P’ng Loke
YR 2020
UL http://biorxiv.org/content/early/2020/07/31/2020.07.31.231308.abstract
AB How the human intestinal immune system is distinctly organized to respond to inflammation is still poorly understood. Here, we used single-cell RNA-sequencing to examine lamina propria CD45+ hematopoietic cells from patients with inflammatory bowel disease that have undergone ileal pouch-anal anastomosis, or the colon mucosa of ulcerative colitis patients. We identified a population of IL1B+ antimicrobial macrophages and FOXP3/+BATF+ T cells that are associated and expanded in inflamed tissues, which we further validated in other scRNA-seq datasets from IBD patients. CD8+ T cells were unexpectedly more abundant in the pouch than colon. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressing IL1B with S100A8/A9 calprotectin as being associated with inflammation, as well as Bacteroides and Escherichia bacterial species. Finally, we find that non-responsiveness to anti-integrin biologic therapies in UC patients is associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions.Competing Interest StatementThe authors have declared no competing interest.