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

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). While many cytokines and their receptors are potently regulated via posttranscriptional mechanisms in response to various stimuli, how CCR6 expression is posttranscriptionally regulated in Th17 cells is unknown. Here, using RNA binding protein HuR conditional knockout (KO) and wild type (WT) mice, we present evidence that HuR posttranscriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR downregulates several microRNA biogenesis which could target the 3 UTR of Ccr6 mRNA for decay. Accordingly, knockout 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.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2twoIfK
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