Analysis of SHIP1 expression and activity in Crohn's disease patients.

Rajesh Somasundaram,Ernst J Kuipers,Frank A Middleton,William G Kerr,Lauran Vogelaar,Jasper J Deuring,C Janneke Van Der Woude,Colin De Haar,Sandra Fernandes,Gwenny M Fuhler,Maikel P Peppelenbosch

doi:10.1371/journal.pone.0182308

Rajesh Somasundaram, Ernst J Kuipers + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0182308

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Journal: PloS one	Publication Date: Aug 2, 2017
Citations: 15	License type: CC BY 4.0

Affiliation: Erasmus MC, SUNY Upstate Medical University

Abstract

BackgroundSH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn’s disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients.MethodsSHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880.ResultsSHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort.ConclusionsAberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.

Highlights

SH2 domain-containing inositol-5’-phosphatase 1 (SHIP1) protein levels are profoundly diminished in a subset of patients; SHIP1 activity and expression are not correlated to ATG16L1 single nucleotide polymorphism (SNP) status in this adult cohort
Aberrant SHIP1 activity can contribute to disease in a subset of adult Crohn’s disease (CD) patients, and warrants further investigation
The SH2 domain-containing inositol-5’-phosphatase 1 (SHIP1), predominantly expressed in hematopoietic tissues [1], is required for the regulation of immune cell compartments, lymphoid and innate immune cell function and intestinal fibrosis [2,3].We and others have shown that SHIP1-/- mice spontaneously develop an intestinal inflammatory phenotype resembling the inflammatory bowel syndrome (IBD) Crohn’s disease (CD), with increased granulocyte infiltration and a profound T cell depletion observed in the small intestine [4,5]

Summary

Introduction

The SH2 domain-containing inositol-5’-phosphatase 1 (SHIP1), predominantly expressed in hematopoietic tissues [1], is required for the regulation of immune cell compartments, lymphoid and innate immune cell function and intestinal fibrosis [2,3].We and others have shown that SHIP1-/- mice spontaneously develop an intestinal inflammatory phenotype resembling the inflammatory bowel syndrome (IBD) Crohn’s disease (CD), with increased granulocyte infiltration and a profound T cell depletion observed in the small intestine [4,5]. While enhanced SHIP1 mRNA expression was observed in biopsies from CD patients [8], Ngoh and colleagues recently demonstrated decreased SHIP1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and biopsies in a cohort consisting mainly of treatment-naive subjects with ileal CD [9,10]. This downregulation was correlated with the presence of a single nucleotide polymorphism (SNP) in the ATG16L1 gene, one of the best described CD risk genes, which lies adjacent to the SHIP1 gene, INPP5D. We studied SHIP1 activity and expression in an adult cohort of CD patients

Methods

Results

Conclusion