Email updates

Keep up to date with the latest news and content from BMC Immunology and BioMed Central.

Open Access Highly Accessed Research article

Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation

Zichen Li12, Ke Li1, Lin Zhu2*, Quancheng Kan2, Yaping Yan1, Priyanka Kumar1, Hui Xu1, Abdolmohamad Rostami1 and Guang-Xian Zhang1*

Author Affiliations

1 Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA

2 Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Henan, China

For all author emails, please log on.

BMC Immunology 2013, 14:20  doi:10.1186/1471-2172-14-20

Published: 23 April 2013

Abstract

Background

IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system.

Methods

We first detected IL-17 receptor expression in NSCs with immunostaining and real time PCR. We then cultured NSCs with IL-17 and determined NSC proliferation by neurosphere formation capability and cell number count, differentiation by immunostaining neural specific markers, and apoptosis of NSCs by flow cytometry.

Results

NSCs constitutively express IL-17R, and when the IL-17R signal pathway was activated by adding IL-17 to NSC culture medium, the number of NSCs was significantly reduced and their ability to form neurospheres was greatly diminished. IL-17 inhibited NSC proliferation, but did not induce cytotoxicity or apoptosis. IL-17 hampered the differentiation of NSCs into astrocytes and oligodendrocyte precursor cells (OPCs). The effects of IL-17 on NSCs can be partially blocked by p38 MAPK inhibitor.

Conclusions

IL-17 blocks proliferation of NSCs, resulting in significantly reduced numbers of astrocytes and OPCs. Thus, in addition to its proinflammatory role in the immune system, IL-17 may also play a direct role in blocking remyelination and neural repair in the CNS.

Keywords:
NSCs; IL-17