The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells.

Authors

Jing Chen, Thomas Jefferson University; Arkansas State University; University of MissouriFollow
Jennifer L. Martindale, National Institutes of HealthFollow
Carole Cramer, Arkansas State University
Myriam Gorospe, National Institutes of HealthFollow
Ulus Atasoy, University of Missouri
Paul D. Drew, University of Arkansas for Medical Sciences
Shiguang Yu, Arkansas State UniversityFollow

Document Type

Article

Publication Date

9-1-2017

Comments

This research was originally published in Journal of Biological Chemistry. Chen, J., Martindale, J. L., Cramer, C., Gorospe, M., Atasoy, U., Drew, P. D., & Yu, S.. The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells. Journal of Biological Chemistry. 2017; 292(35):14532-14543. © the American Society for Biochemistry and Molecular Biology.

Abstract

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA expressions, which could target the 3'-UTR of Ccr6 mRNA for decay. Accordingly, knock-out of HuR reduced CCR6 expression on Th17 cells and impaired their migration to CNS compared with the response of WT Th17 cells and thereby ameliorated EAE. Together, these findings highlight how HuR contributes to Th17 cell-mediated autoimmune neuroinflammation and support the notion that targeting HuR might be a potential therapeutic intervention for managing autoimmune disorders of the CNS.

Recommended Citation

Chen, Jing; Martindale, Jennifer L.; Cramer, Carole; Gorospe, Myriam; Atasoy, Ulus; Drew, Paul D.; and Yu, Shiguang, "The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells." (2017). Department of Neurology Faculty Papers. Paper 136.
https://jdc.jefferson.edu/neurologyfp/136

PubMed ID

28684423