Published online Mar 21, 2018. doi: 10.3748/wjg.v24.i11.1196
Peer-review started: December 21, 2017
First decision: January 18, 2018
Revised: January 29, 2018
Accepted: February 1, 2018
Article in press: February 1, 2018
Published online: March 21, 2018
In Crohn’s disease (CD), the interplay of genetic and environmental factors converges at the level of an altered antipathogenic immune response, which is incompletely understood. Peripheral blood mononuclear cells (PBMCs) provide a useful tool to study elements of the immunopathogenesis of the disease in vitro.
Currently, there is a lack of biomarkers to predict the clinical course of CD. Furthermore, the development of specific therapies would benefit from an improved mechanistic understanding of the pathogenesis of the disease.
The aim of this study was to identify disease-specific gene expression profiles of PBMCs from patients with CD in clinical remission. Specifically, we were interested in alterations of the gene expression profile after challenging PBMCs with pathogen-associated molecular patterns (PAMPs) and the immunomodulatory hormone vitamin D.
PBMCs from patients with CD and healthy donors were cultured with vitamin D, peptidoglycan (PGN) and lipopolysaccharide (LPS), before RNA was isolated and subjected to microarray analysis and quantitative real-time PCR. Disease-specific gene expression profiles were evaluated by general linear model repeated measure analysis, paying particular attention to the well-established CD risk gene NOD2.
Microarray experiments yielded a total of 267 genes that were significantly up- or downregulated in PBMCs of patients with CD, compared to healthy donors, after challenge with vitamin D and/or a combination of LPS and PGN. For further analysis by real-time PCR, genes with roles in inflammation and immunity were selected. For three of these genes, CLEC5A, lysozyme and TREM1, a disease-associated expression pattern was validated. Six genes, including CLEC5A and lysozyme, were found to be expressed in a NOD2-dependent manner.
PBMCs of patients with CD display alterations of their response to vitamin D and PAMPs that are preserved even at the stage of clinical remission. CLEC5A, TREM1 and NOD2 may act in a common network relevant to CD pathogenesis.
Follow-up studies on alterations of the antipathogenic immune response may provide novel insights into the pathogenesis of CD and may also help to establish biomarkers to better predict the clinical course of the disease.