Journal ArticleDOI
Knockout of P2Y12 aggravates experimental autoimmune encephalomyelitis in mice via increasing of IL-23 production and Th17 cell differentiation by dendritic cells
Jiang Zhang,Zhenlong Li,Xuefei Hu,Qiong Su,Cong He,Jing Liu,Hua Ren,Min Qian,Junling Liu,Shufang Cui,Wenzheng Jiang +10 more
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TLDR
It is demonstrated that genetic deletion of P2Y12 receptor broke the balance of Th subtypes by affecting the cytokine profile of BMDCs and resulted in the aggravated EAE, which suggested that P2y12 may be a potential target in treating MS.Abstract:
Experimental autoimmune encephalomyelitis (EAE), a common model of multiple sclerosis (MS), is mainly mediated by CD4+ T cells with demyelination and neurodegeneration of central nervous system (CNS). The loss of P2Y12 receptor might be associated with the pathogenesis of MS/EAE, but its potential mechanism is still not clear. In this study, more severe EAE developed in P2Y12-knockout (P2Y12-KO) mice compared to WT mice. Knockout of P2Y12 increased expression of IL-17A in the sera and proportion of Th17 cells in spleen and CNS. However, in vitro studies showed that P2Y12 did not influence cell differentiation and proliferation of CD4+ T cells. In bone marrow-derived dendritic cells (BMDCs), loss of P2Y12 significantly increased the production of IL-23 in contrast to the wild-type (WT) BMDCs. FACS analysis indicated that the culture supernatant from P2Y12-deficient DCs promoted more naive CD4+ T cells to differentiate into Th17 cells. Our finding demonstrated that genetic deletion of P2Y12 receptor broke the balance of Th subtypes by affecting the cytokine profile of BMDCs and resulted in the aggravated EAE, which suggested that P2Y12 may be a potential target in treating MS.read more
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Journal ArticleDOI
The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.
TL;DR: The possible therapeutic applications of drugs acting on purinergic pathways, which have been entering clinical development, to manage patients suffering from IMIDs are discussed.
Journal ArticleDOI
Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy.
Ágatha Oliveira-Giacomelli,Yahaira Naaldijk,Laura Sardá-Arroyo,Maria C. Gonçalves,Juliana Corrêa-Velloso,Micheli M. Pillat,Hellio Danny Nóbrega de Souza,Henning Ulrich +7 more
TL;DR: This review analyzes currently available data, which suggests involvement of the purinergic system in neuro-associated motor dysfunctions and underlying mechanisms and possible targets for pharmacological interventions.
Book ChapterDOI
P2Y Receptors in Immune Response and Inflammation
Diana Le Duc,Angela Schulz,Vera Lede,Annelie Schulze,Doreen Thor,Antje Brüser,Torsten Schöneberg +6 more
TL;DR: A perspective on the P2y receptors' molecular structure and physiological importance in immune cells, as well as the related diseases and P2Y-targeting therapies, are given.
Journal ArticleDOI
Purinergic receptors in multiple sclerosis pathogenesis.
TL;DR: Emerging evidence of the role of these three receptor types as potential MS biomarkers and therapeutic targets is summarized.
Book ChapterDOI
Structure, Pharmacology and Roles in Physiology of the P2Y 12 Receptor
TL;DR: There is evidence for changes in P2Y12 receptor expression in CNS pathologies including Alzheimer’s diseases and multiple sclerosis, and the recently published three-dimensional crystal structures of the human P2y12 receptor in complex with agonists and antagonists will facilitate the development of novel therapeutic agents with reduced adverse effects.
References
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