Open AccessP2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis
Author(s) -
Zabala Alazne,
VazquezVilloldo Nuria,
Rissiek Björn,
Gejo Jon,
Martin Abraham,
Palomino Aitor,
PerezSamartín Alberto,
Pulagam Krishna R,
Lukowiak Marco,
CapetilloZarate Estibaliz,
Llop Jordi,
Magnus Tim,
KochNolte Friedrich,
Rassendren Francois,
Matute Carlos,
Domercq María
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708743
Subject(s) - microglia , remyelination , autoimmune encephalitis , receptor , immunology , neuroscience , encephalitis , medicine , chemistry , microbiology and biotechnology , virology , biology , inflammation , central nervous system , myelin , virus
Microglia survey the brain microenvironment for signals of injury or infection and are essential for the initiation and resolution of pathogen‐ or tissue damage‐induced inflammation. Understanding the mechanism of microglia responses during pathology is hence vital to promote regenerative responses. Here, we analyzed the role of purinergic receptor P2X4 (P2X4R) in microglia/macrophages during autoimmune inflammation. Blockade of P2X4R signaling exacerbated clinical signs in the experimental autoimmune encephalomyelitis ( EAE ) model and also favored microglia activation to a pro‐inflammatory phenotype and inhibited myelin phagocytosis. Moreover, P2X4R blockade in microglia halted oligodendrocyte differentiation in vitro and remyelination after lysolecithin‐induced demyelination. Conversely, potentiation of P2X4R signaling by the allosteric modulator ivermectin ( IVM ) favored a switch in microglia to an anti‐inflammatory phenotype, potentiated myelin phagocytosis, promoted the remyelination response, and ameliorated clinical signs of EAE . Our results provide evidence that P2X4Rs modulate microglia/macrophage inflammatory responses and identify IVM as a potential candidate among currently used drugs to promote the repair of myelin damage.