Interleukin 17A Promotes Lymphocytes Adhesion and Induces CCL2 and CXCL1 Release from Brain Endothelial Cells.

Dagmara Wojkowska,Piotr Szpakowski,Andrzej Glabinski

doi:10.3390/ijms18051000

Dagmara Wojkowska, Piotr Szpakowski + Show 1 more

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https://doi.org/10.3390/ijms18051000

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Abstract

The nature of the interaction between Th17 cells and the blood–brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). Tumor necrosis factor alpha (TNF-α) or interleukin 17 (IL-17) stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express Vascular cell adhesion molecule 1 (VCAM-1), the receptor responsible for inflammatory cell adhesion, which binds very late antigen 4 (VLA-4) on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-α and IL-17 on the adherence of Th17 cells to bEnd.3. The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

Highlights

Multiple sclerosis (MS) is a neurological disease wherein the myelin and neurons of the brain and spinal cord are destroyed by the immune system, a process believed to be mediated by CD4+ T cells [1,2]
Our results suggest that interleukin 17 (IL-17), a key product of activated Th17 cells, is able to modify the functions of brain endothelial cells: the most important compartment of blood–brain barrier (BBB)
Our findings indicate that Th17 cells strongly adhere to brain endothelial cells following TNF-α stimulation

Summary

Introduction

Multiple sclerosis (MS) is a neurological disease wherein the myelin and neurons of the brain and spinal cord are destroyed by the immune system, a process believed to be mediated by CD4+ T cells [1,2]. Patients suffering from MS have several neurological signs and symptoms including muscle weakness, lack of coordination of movements and sensory disturbances [3]. Th17 cells produce a range of inflammatory cytokines, including interleukin 17 A/F (IL-17A/F), interleukin (IL-21) and interleukin (IL-22), which are involved in the development of inflammatory foci in the CNS, and neutralization of the key cytokine IL-17 ameliorated symptoms in an animal model of MS: experimental autoimmune encephalomyelitis (EAE). The critical step of this process is transmigration of Th17 cells through the blood–brain barrier (BBB) [6,7]

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