Transcriptomic Profiling of Collagenous Colitis Identifies Hallmarks of Nondestructive Inflammatory Bowel DiseaseSummary

Celia Escudero-Hernández; Atle van Beelen Granlund; Torunn Bruland; Arne Kristian Sandvik; Stefan Koch; Ann Elisabet Østvik; Andreas Münch

Cellular and Molecular Gastroenterology and Hepatology (Jan 2021)

Transcriptomic Profiling of Collagenous Colitis Identifies Hallmarks of Nondestructive Inflammatory Bowel DiseaseSummary

Celia Escudero-Hernández,
Atle van Beelen Granlund,
Torunn Bruland,
Arne Kristian Sandvik,
Stefan Koch,
Ann Elisabet Østvik,
Andreas Münch

Affiliations

Celia Escudero-Hernández: Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Correspondence Address correspondence to: Celia Escudero Hernández, PhD, Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University-Kiel, and University Hospital Schleswig-Holstein, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Atle van Beelen Granlund: Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Torunn Bruland: Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Clinic of Medicine, St Olav’s University Hospital, Trondheim, Norway
Arne Kristian Sandvik: Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Clinic of Medicine, St Olav’s University Hospital, Trondheim, Norway; Department of Gastroenterology and Hepatology, St Olav’s University Hospital, Trondheim, Norway
Stefan Koch: Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden
Ann Elisabet Østvik: Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Clinic of Medicine, St Olav’s University Hospital, Trondheim, Norway; Department of Gastroenterology and Hepatology, St Olav’s University Hospital, Trondheim, Norway
Andreas Münch: Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden; Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden

Journal volume & issue: Vol. 12, no. 2
pp. 665 – 687

Abstract

Read online

Background and Aims: The pathophysiology of the inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of mucosal samples from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and control subjects to gain insight into CC pathophysiology, identify genetic signatures linked to CC, and uncover potentially druggable disease pathways. Methods: We performed whole transcriptome sequencing of CC samples from patients before and during treatment with the corticosteroid drug budesonide, CC steroid-refractory patients, UC patients, and healthy control subjects (n = 9–13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell (IEC) gene expression were analyzed by gene set enrichment and gene set variation analyses to identify significant pathways and cells, respectively, altered in CC. Leading genes and cells were validated using reverse-transcription quantitative polymerase chain reaction or immunohistochemistry. Results: We identified an activation of the adaptive immune response to bacteria and viruses in active CC that could be mediated by dendritic cells. Moreover, IECs display hyperproliferation and increased antigen presentation in active CC. Further analysis revealed that genes related to the immune response (DUOX2, PLA2G2A, CXCL9), DNA transcription (CTR9), protein processing (JOSD1, URI1), and ion transport (SLC9A3) remained dysregulated even after budesonide-induced remission. Budesonide-refractory CC patients fail to restore normal gene expression, and displayed a transcriptomic profile close to UC. Conclusions: Our study confirmed the implication of innate and adaptive immune responses in CC, governed by IECs and dendritic cells, respectively, and identified ongoing epithelial damage. Refractory CC could share pathomechanisms with UC.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

About the journal

Abstract

Keywords