GPCR183
GPCR183, or EBI2, is a member of the rhodopsin‐like subfamily of class A
transmembrane spanning GPCRs (Daugvilaite, Arfelt, Benned-Jensen, Sailer
& Rosenkilde, 2014). It expressed on the surface of immune cells
including T-lymphocytes, monocytes, dendritic cells, astrocytes and
innate lymphoid cells (Duc, Vigne & Pot, 2019). GPCR183 is believed to
act as a chemoattractant receptor participating in the migration of
immune cells down a gradient towards 7α,25-diHC or 7α,(25R)26-diHC
(Hannedouche et al., 2011; Liu et al., 2011). Importantly, inflamed
white matter of multiple sclerosis patients shows a high expression of
GPCR183 compared to non-inflamed white matter (Clottu et al., 2017) and
7α,25-diHC has been found to be increased in spinal cord during EAE
development, a mouse model of multiple sclerosis (Wanke et al., 2017),
linking GPCR183, its neuro-oxysterol ligand, immune cell migration and
multiple sclerosis. Importantly, GPCR183 is expressed by Th17 cells
during inflammation and infiltrating cells in multiple sclerosis lesions
express GPCR183 (Wanke et al., 2017). Furthermore, expression of
cholesterol 25-hydroxylase (CH25H) and CYP7B1, two enzymes involved in
7α,25-diHC biosynthesis (Figure 1), was found to change during the
course of EAE with strong up-regulation in spinal cord leading to
increased concentration of 7α,25-diHC (Wanke et al., 2017). Remarkably,
microglia express CH25H early in EAE, while CYP7B1 is expressed by
infiltrating monocytes and lymphocytes (Wanke et al., 2017). This data
leads to the conclusion that GPCR183 and 7α,25-diHC play a role in the
migration of inflammatory CD4+ T cells into the CNS.
7α,(25R)26-diHC is also a GPCR183 ligand and it is perhaps no
coincidence that this molecule is also an agonist towards RORγt.