Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor

Authors: Joel Kaye, Victor Piryatinsky, Tal Birnberg, Tal Hingaly, Emanuel Raymond, Rina Kashi, Einat Amit‐Romach, Ignacio Caballero, Fadi Towfic, Mark A. Ator, Efrat Rubinstein, Daphna Laifenfeld, Aric Orbach, Doron Shinar, Yael Marantz, Iris Grossman, Volker Knappertz, Michael R. Hayden, Ralph Laufer - Proceedings of the National Academy of Sciences, PNAS 2016 cited by 140

Significance Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis as well as Huntington’s disease. It is thought that laquinimod has a primary effect on the peripheral innate immune system and also acts directly on resident cells within the CNS. However, the exact mechanism of action of laquinimod has not been fully elucidated. We investigated gene expression in laquinimod-treated mice and show induction of genes downstream to activation of the aryl hydrocarbon receptor (AhR). In this paper, we examine the role of the AhR in laquinimod treatment of experimental autoimmune encephalomyelitis and demonstrate that AhR is the molecular target of laquinimod in this model.