Inhibition of phosphoinositide 3-kinase delta attenuates experimental autoimmune encephalomyelitis in mice
Shi-Qiang Shang1, Jian Li2, Shu-Qing Li3
1Department of Rehabilitation Medicine, Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.
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.
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.
