Receptor-Type Protein-Tyrosine Phosphatase ζ and Colony Stimulating Factor-1 Receptor in the Intestine: Cellular Expression and Cytokine- and Chemokine Responses by Interleukin-34 and Colony Stimulating Factor-1.

Stephanie Zwicker,Sven Almer,Daniela Bureik,Gisele Lago Martinez,Madeleen Bosma,Elisabeth A Boström,Ashlesh K Murthy

doi:10.1371/journal.pone.0167324

Stephanie Zwicker, Sven Almer + Show 5 more

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https://doi.org/10.1371/journal.pone.0167324

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Journal: PloS one	Publication Date: Nov 29, 2016
Citations: 17	License type: CC BY 4.0

Affiliation: Karolinska Institutet

Abstract

Differential intestinal expression of the macrophage growth factors colony stimulating factor-1 (CSF-1), interleukin (IL)-34, and their shared CSF-1 receptor (CSF-1R) in inflammatory bowel disease (IBD) has been shown. Diverse expression between CSF-1 and IL-34, suggest that IL-34 may signal via an alternate receptor. Receptor-type protein-tyrosine phosphatase ζ (PTPRZ1, RPTP-ζ), an additional IL-34 receptor, was recently identified. Here, we aimed to assess PTPRZ1 expression in IBD and non-IBD intestinal biopsies. Further, we aimed to investigate cellular PTPRZ1 and CSF-1R expression, and cytokine- and chemokine responses by IL-34 and CSF-1. The expression of PTPRZ1 was higher in non-IBD colon compared to ileum. PTPRZ1 expression was not altered with inflammation in IBD, however, correlated to IL34, CSF1, and CSF1R. The expression patterns of PTPRZ1 and CSF-1R differed in peripheral blood mononuclear cells (PBMCs), monocytes, macrophages, and intestinal epithelial cell line. PBMCs and monocytes of the same donors responded differently to IL-34 and CSF-1 with altered expression of tumor-necrosis factor α (TNF-α), IL-1β, interferon γ (IFN-γ), IL-13, IL-8, and monocyte chemotactic protein-1 (MCP-1) levels. This study shows that PTPRZ1 was expressed in bowel tissue. Furthermore, CSF-1R protein was detected in an intestinal epithelial cell line and donor dependently in primary PBMCs, monocytes, and macrophages, and first hints also suggest an expression in these cells for PTPRZ1, which may mediate IL-34 and CSF-1 actions.

Highlights

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal tract that are collectively referred to as inflammatory bowel disease (IBD)
PTPRZ1 expression is higher in colon compared to ileum of non-IBD subjects but is not altered in IBD patients compared to non-IBD subjects
PTPRZ1 expression was not altered with inflammation in IBD-patients (Fig 1E)

Summary

Introduction

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal tract that are collectively referred to as inflammatory bowel disease (IBD). Our group and Franzeet al., reported regulation of IL-34 and CSF-1 with inflammation in IBD [8, 9]. We reported different expression patterns of IL-34 and CSF-1 in ileum and colon of non-IBD subjects, higher CSF-1R expression in sigmoid compared to transverse colon, and up-regulated CSF-1R expression with inflammation in IBD patients [8]. In addition to the gut, CSF-1R is detected in other tissues including the brain, liver and heart [10]. An additional receptor of IL-34, receptor-type protein-tyrosine phosphatase z (PTPRZ1, RPTP-z), was recently identified by Nandi and colleagues who showed signalling through PTPRZ1 by IL-34, but not CSF-1, in mouse brain and in the human glioblastoma cell line U251 [11]. PTPRZ1 is expressed in different tissues including the brain, stomach, and small intestine, according to the human protein atlas database [10]. The expression and regulation of PTPRZ1 in the gut has not been characterized in detail to date

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