Reduced ErbB4 Expression in Immune Cells of Patients with Relapsing Remitting Multiple Sclerosis

Evgenia Tynyakov-Samra,Eitan Auriel,Arnon Karni,Yifat Levy-Amir

doi:10.1155/2011/561262

Evgenia Tynyakov-Samra, Eitan Auriel + Show 2 more

Open Access

https://doi.org/10.1155/2011/561262

Copy DOI

Abstract

Background. There is an insufficient remyelination in the lesions of multiple sclerosis (MS). One of the factor that was found to promote remyelination is neuregulin-1 which is the ligand of ErbB4. Immune cells have been implicated in neurogenesis and oligodendrogenesis. Aims. We studied the expression of ErbB4 in the immune cells of patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls. Methods. ErB4 expression in immune cells was studied by flow cytometry without stimulation or with stimulation with anti-CD3 and anti-CD28 monoclonal antibodies or in the presence of interferon-g or TNF-α as well as by immunoprecipitation and Western blot, and its mRNA was studied by real-time PCR. Results. We found reduced levels of ErbB4 in the total PBMCs and in T cells, monocytes, and B cells of RR MS patients. Similarly, the ErbB4 RNA levels were reduced in the immune cells of patients with RR-MS. Stimulation via CD3 and CD28 significantly upregulated the expression of ErbB4 on immune cells healthy individuals. This effect was weaker in the patients group. Conclusion. ErbB4 may play a role in the proliferation of oligodendrocyte progenitor cells, differentiation of oligodendrocytes, and remyelination, and, therefore, the reduced ErbB4 expression in immune cells of patients with RR-MS may contribute to insufficient remyelination that occurs in the disease.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that is responsible for the most common cause of neurological disability in young adults [1]
We found that the mean fluorescence intensity (MFI) of ErbB4 expression in T cells was lower in relapsing remitting (RR)-multiple sclerosis (MS) patients (22.2 ± 3.3) than in healthy controls (HC) (37.5 ± 2.4, P = 0.002), the MFI of ErbB4 expression in monocytes was lower in relapsing remitting MS (RR-MS) patients (88.5 ± 11.5) as compared to HC (135.7 ± 8.9, P = 0.006), and the ErbB4 expression in B cells was lower in RR-MS patients (39.8 ± 4.9) as compared to HC (56.2 ± 3.9, P = 0.018)
We looked for the expression of the natural receptor of neuregulins, ErbB4, and found for the first time that ErbB4 levels are reduced in the Peripheral blood mononuclear cells (PBMCs) of patients with RR-MS

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that is responsible for the most common cause of neurological disability in young adults [1]. We studied the expression of ErbB4 in the immune cells of patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls. The ErbB4 RNA levels were reduced in the immune cells of patients with RR-MS. Stimulation via CD3 and CD28 significantly upregulated the expression of ErbB4 on immune cells healthy individuals. This effect was weaker in the patients group. ErbB4 may play a role in the proliferation of oligodendrocyte progenitor cells, differentiation of oligodendrocytes, and remyelination, and, the reduced ErbB4 expression in immune cells of patients with RR-MS may contribute to insufficient remyelination that occurs in the disease

Objectives

Methods

Conclusion