TY - JOUR AU - Chen, Hui AU - Assmann, Julian C. AU - Krenz, Antje AU - Rahman, Mahbubur AU - Grimm, Myriam AU - Karsten, Christian M. AU - Köhl, Jörg AU - Offermanns, Stefan AU - Wettschureck, Nina AU - Schwaninger, Markus T1 - Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE PY - 2014/05/01/ AB - Taken orally, the drug dimethyl fumarate (DMF) has been shown to improve functional outcomes for patients with MS; however, it is unclear how DMF mediates a protective effect. DMF and, more so, its active metabolite, monomethyl fumarate, are known agonists of the hydroxycarboxylic acid receptor 2 (HCA2), a G protein–coupled membrane receptor. Here, we evaluated the contribution of HCA2 in mediating the protective effect afforded by DMF in EAE, a mouse model of MS. DMF treatment reduced neurological deficit, immune cell infiltration, and demyelination of the spinal cords in wild-type mice, but not in Hca2–/– mice, indicating that HCA2 is required for the therapeutic effect of DMF. In particular, DMF decreased the number of infiltrating neutrophils in a HCA2-dependent manner, likely by interfering with neutrophil adhesion to endothelial cells and chemotaxis. Together, our data indicate that HCA2 mediates the therapeutic effects of DMF in EAE. Furthermore, identification of HCA2 as a molecular target may help to optimize MS therapy. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI72151 VL - 124 IS - 5 UR - https://doi.org/10.1172/JCI72151 SP - 2188 EP - 2192 PB - The American Society for Clinical Investigation ER -