Research

Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis

Jayasri Das Sarma^1,3 , Bogoljub Ciric¹ , Ryan Marek¹ , Sanjoy Sadhukhan¹ , Michael L Caruso¹ , Jasmine Shafagh¹ , Denise C Fitzgerald¹ , Kenneth S Shindler² and AM Rostami¹

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

²  Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, Philadelphia, PA 19104, USA

³  Indian Institute of Science Education and Research-Kolkata (IISER-K), HC-VII, Sector-III, Salt Lake, Kolkata-700-106, India

author email corresponding author email

Journal of Neuroinflammation 2009, 6:14doi:10.1186/1742-2094-6-14

Published:	28 April 2009

Abstract

Background

Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

Methods

EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA.

Results

Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.

Conclusion

IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions.