Abstract
Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.
Highlights
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) and is the most common neurological disorder affecting young adults [1]
Pro-inflammatory role for the proton-sensing G protein-coupled receptors (GPCRs), Ovarian cancer G protein-coupled receptor 1 (OGR1), in a variety of diseases including allergy and cancer; whether this molecule has a similar role in autoimmunity had not been examined
We explored the role of OGR1 in the development of EAE and observed that OGR1-KO mice exhibited a striking attenuation of CNS inflammation during EAE that associated with a reduced expansion of MOG35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effector cells in the CNS
Summary
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) and is the most common neurological disorder affecting young adults [1]. It is generally thought that the incident attack of MS occurs when an unknown environmental agent triggers the activation and T helper 1 (Th1) and Th17 differentiation of myelin-reactive T cells in peripheral lymphoid organs. Upon trafficking to the CNS, pathogenic Th1 and Th17 cells secrete pro-inflammatory cytokines and chemokines that activate resident microglia and PLOS ONE | DOI:10.1371/journal.pone.0148439. Upon trafficking to the CNS, pathogenic Th1 and Th17 cells secrete pro-inflammatory cytokines and chemokines that activate resident microglia and PLOS ONE | DOI:10.1371/journal.pone.0148439 February 1, 2016
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