Detailed Transcriptional Landscape of Peripheral Blood Points to Increased Neutrophil Activation in Treatment-Naïve Inflammatory Bowel Disease

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Simonas Juzenas - (Autor:in)
  • Matthias Huebenthal - (Autor:in)
  • Carl Marten Lindqvist - (Autor:in)
  • Robert Kruse - (Autor:in)
  • Tim Alexander Steiert - (Autor:in)
  • Frauke Degenhardt - (Autor:in)
  • Dominik Schulte - (Autor:in)
  • Susanna Nikolaus - (Autor:in)
  • Sebastian Zeissig - , Professur für Mukosale Immunologie (Autor:in)
  • Daniel Bergemalm - (Autor:in)
  • Sven Almer - (Autor:in)
  • Henrik Hjortswang - (Autor:in)
  • Francesca Bresso - (Autor:in)
  • Nina Struening - (Autor:in)
  • Juozas Kupcinskas - (Autor:in)
  • Andreas Keller - (Autor:in)
  • Wolfgang Lieb - (Autor:in)
  • Philip Rosenstiel - (Autor:in)
  • Stefan Schreiber - , Professur für Festkörperelektronik (Autor:in)
  • Mauro D'Amato - (Autor:in)
  • Jonas Halfvarson - (Autor:in)
  • Georg Hemmrich-Stanisak - (Autor:in)
  • Andre Franke - (Autor:in)

Abstract

Background and Aims: Inflammatory bowel disease [IBD] is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease [CD] or ulcerative colitis [UC]. These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and, thus, common immune regulatory pathways. Methods: Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve [n = 110] and treatment-exposed [n = 177] IBD patients as well as symptomatic [n = 65] and healthy controls [n = 95]. Results: Broadly, the peripheral blood transcriptomes of CD and UC patients were similar. However, there was an extensive gene deregulation in the blood of IBD patients, while only a slight deregulation in symptomatic controls, when compared with healthy controls. The deregulated mRNAs and miRNAs are mainly involved in the innate immunity and are especially enriched in neutrophil activation-related pathways. Oxidative phosphorylation and neutrophil activation-related modules were found to be differentially co-expressed among treatment-naïve IBD as compared to healthy controls. In the deregulated neutrophil activation-related co-expression module, IL1B was identified as the central gene. Levels of co-expression among IL1B and chemosensing receptor [CXCR1/2 and FPR1/2] genes were reduced in the blood of IBD patients when compared with healthy controls. Conclusions: Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation.

Details

OriginalspracheEnglisch
Seiten (von - bis)1097-1109
Seitenumfang13
FachzeitschriftJournal of Crohn's and colitis
Jahrgang16
Ausgabenummer7
PublikationsstatusVeröffentlicht - 1 Juli 2022
Peer-Review-StatusJa

Externe IDs

WOS 000760458900001
Scopus 85132374171
PubMed 35022690
unpaywall 10.1093/ecco-jcc/jjac003
Mendeley 6122c39e-2a8d-3a1c-99ee-ef2c2317b1fe

Schlagworte

Schlagwörter

  • Colitis, Ulcerative, Crohn Disease, Humans, Inflammatory Bowel Diseases/metabolism, MicroRNAs/genetics, Neutrophil Activation/genetics, RNA, Messenger/genetics, Transcriptome

Bibliotheksschlagworte