Central Nervous System and Peripheral Expression of CCL19, CCL21 and Their Receptor CCR7 in Experimental Model of Multiple Sclerosis.

Bartosz Bielecki,Andrzej Glabinski,Pawel Wolinski,Andrzej Bednarek,Izabela Jatczak-Pawlik

doi:10.1007/s00005-015-0339-9

Abstract

It is well documented that inflammatory chemokines play a significant role in the development of multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE). Recently, the involvement of homeostatic (or lymphoid) chemokines in the pathogenesis of autoimmune diseases has become an object of intensive study. In this work, quantitative analysis of CCL19, CCL21 and CCR7 expression in the central nervous system (CNS), as well as in inflammatory mononuclear cells isolated from several organs during the first attack, remission and the second attack of chronic-relapsing EAE (ChREAE), was performed. Using real-time PCR, RNAse Protection Assay and immunohistochemistry, the expression of both chemokines, as well as of their common receptor CCR7, was analyzed in the brain, spleen, lymph nodes and peripheral blood mononuclear cells. Increased expression of CCL19 and CCL21 was observed mostly in mononuclear inflammatory cells isolated from the CNS during active ChREAE. At the same time the expression of CCR7 in blood mononuclear leukocytes was reduced. This observation extends our current knowledge about the possible role of chemokines CCL19, CCL21 and their receptor CCR7 in the pathogenesis of ChREAE and, by extension, MS.

Highlights

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) affecting predominantly young adults
Further analysis showed that the expression of CCL19 in the CNS was upregulated in brain homogenates during the first attack of the disease (p = 0.02) (Fig. 1)
In contrast to CCL19, the expression of CCL21 in peripheral blood mononuclear cells (PBMCs) obtained from animals with the first attack of chronicrelapsing EAE (ChREAE) was not upregulated (Fig. 4), in the mononuclear cells isolated from the CNS at that time we observed a significant increase of CCL21 expression in comparison to normal controls (p \ 0.001)

Summary

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) affecting predominantly young adults. It is characterized by a diverse clinical picture and a complex physiopathology. In order to better understand the immunopathology of MS, various experimental models have been established with the most renowned being experimental autoimmune encephalomyelitis (EAE). A clinical resemblance to the most common form of MS, relapsing-remitting MS, makes chronic-relapsing type of EAE (ChREAE) a attractive model. It helps to study the sequence of events leading to a development of neuroinflammation as well as the relation between clinical signs and reactivation of CNS inflammation. It has been shown that the clinical course of EAE correlates well with changes of expression of proinflammatory and immunomodulatory cytokines and chemokines in the brain and spinal cord (Glabinski et al 2003b)

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