title: Inhibition of phosphoinositide 3-kinase delta attenuates experimental autoimmune encephalomyelitis in mice.
abstract: The phosphoinositide 3-kinase delta (PI3Kδ) has been implicated in multiple signaling pathways involved in autoimmune diseases. We here aimed to test the hypothesis that selective inhibition of PI3Kδ may promote anti-inflammatory effects by inhibiting Th1 and Th17 cells. We investigated the therapeutic efficacy of a selective PI3Kδ inhibitor IC87114 in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The efficacy was evaluated based on clinical scores, histopathology, serum cytokines and inflammatory infiltrations in the central nervous system (CNS). Treatment of EAE mice with IC87114 reduced the clinical symptoms, histopathology and cellular infiltration into the CNS. And treatment of EAE with IC87114 suppressed the Th1 and Th17 cell ratios. Consistently, the serum levels of IL-1β, IL-6, IL-17 and INF-γ were markedly reduced by IC87114. Taken together, our studies demonstrate that inhibition of PI3Kδ may serve as novel therapy to suppress neuroinflammation seen during EAE.
authors.affiliation: Department of Rehabilitation Medicine, Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Shang
authors.affiliation: Department of Neurosurgery, Taian Central Hospital Taian 271000, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University Jinan 250014, Shandong, China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Li
authors.affiliation: Department of Neurology, Jining First People's Hospital Jining 272011, Shandong, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Cao
keywords: Experimental autoimmune encephalomyelitis; Th1; Th17; multiple sclerosis; phosphoinositide 3-kinase delta