Importance of TLR9-IL23-IL17 axis in inflammatory bowel disease development: Gene expression profiling study

Sanja Dragasevic; Biljana Stankovic; Aleksandra Sokic-Milutinovic; Tomica Milosavljevic; Tamara Milovanovic; Snezana Lukic; Sanja Srzentic Drazilov; Kristel Klaassen; Nikola Kotur; Sonja Pavlovic; Dragan Popovic

doi:10.1016/j.clim.2018.09.001

Importance of TLR9-IL23-IL17 axis in inflammatory bowel disease development: Gene expression profiling study

Clin Immunol. 2018 Dec:197:86-95. doi: 10.1016/j.clim.2018.09.001. Epub 2018 Sep 5.

Affiliations

¹ Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Koste Todorovica 2, 11000 Belgrade, Serbia.
² Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia.
³ Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Koste Todorovica 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
⁴ Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. Electronic address: sanja.srzentic@imgge.bg.ac.rs.
⁵ Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. Electronic address: kristel.klaassen@imgge.bg.ac.rs.
⁶ Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. Electronic address: nikola.kotur@imgge.bg.ac.rs.
⁷ Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. Electronic address: sonya@sezampro.rs.
⁸ Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Koste Todorovica 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia. Electronic address: dragan.drendo23@gmail.com.

PMID: 30193869
DOI: 10.1016/j.clim.2018.09.001

Abstract

Background and aims: Mucosal gene expression have not been fully enlightened in inflammatory bowel disease (IBD). Aim of this study was to define IL23A, IL17A, IL17F and TLR9 expression in different IBD phenotypes.

Methods: Evaluation of mRNA levels was performed in paired non-inflamed and inflamed mucosal biopsies of newly diagnosed 50 Crohn's disease (CD) and 54 ulcerative colitis (UC) patients by quantitative real-time PCR analysis.

Results: IL17A and IL17F expression levels were significantly increased in inflamed IBD mucosa. Inflamed CD ileal and UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed increased TLR9 mRNA level. Correlation between analysed mRNAs levels and endoscopic and clinical disease activity were found in UC, but only with clinical activity in CD.

Conclusion: Both CD and UC presented expression of Th17-associated genes. Nevertheless, expression profiles between different disease forms varies which should be taken into account for future research and therapeutics strategies.

Keywords: Expression profiling; IL23/ IL17/TLR9; Inflammatory bowel disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Colitis, Ulcerative / genetics*
Colitis, Ulcerative / immunology
Colitis, Ulcerative / metabolism
Colon / immunology
Colon / metabolism
Crohn Disease / genetics*
Crohn Disease / immunology
Crohn Disease / metabolism
Cross-Sectional Studies
Female
Gene Expression Profiling
Humans
Ileum / immunology
Ileum / metabolism
Interleukin-17 / genetics*
Interleukin-17 / immunology
Interleukin-23 Subunit p19 / genetics*
Interleukin-23 Subunit p19 / immunology
Intestinal Mucosa / immunology
Intestinal Mucosa / metabolism
Male
Middle Aged
RNA, Messenger / metabolism
Serbia
Signal Transduction
Toll-Like Receptor 9 / genetics*
Toll-Like Receptor 9 / immunology

Substances

IL17A protein, human
IL17F protein, human
IL23A protein, human
Interleukin-17
Interleukin-23 Subunit p19
RNA, Messenger
TLR9 protein, human
Toll-Like Receptor 9