OGR1/GPR68 modulates the severity of experimental autoimmune encephalomyelitis and regulates nitric oxide production by macrophages

Cheryl A. D'Souza, Fei Linda Zhao, Xujian Li, Yan Xu, Shannon E. Dunn, Li Zhang

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0148439
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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autoimmunity
T-cells
Autoimmune Experimental Encephalomyelitis
Macrophages
encephalitis
Autoimmunity
Knockout Mice
nitric oxide
Nitric Oxide
macrophages
T-lymphocytes
T-Lymphocytes
mice
Th17 Cells
Th1 Cells
ovarian neoplasms
myelin sheath
Neurology
dendritic cells
G-Protein-Coupled Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

OGR1/GPR68 modulates the severity of experimental autoimmune encephalomyelitis and regulates nitric oxide production by macrophages. / D'Souza, Cheryl A.; Zhao, Fei Linda; Li, Xujian; Xu, Yan; Dunn, Shannon E.; Zhang, Li.

In: PLoS One, Vol. 11, No. 2, e0148439, 01.02.2016.

Research output: Contribution to journalArticle

D'Souza, Cheryl A. ; Zhao, Fei Linda ; Li, Xujian ; Xu, Yan ; Dunn, Shannon E. ; Zhang, Li. / OGR1/GPR68 modulates the severity of experimental autoimmune encephalomyelitis and regulates nitric oxide production by macrophages. In: PLoS One. 2016 ; Vol. 11, No. 2.
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