7α,25-dihydroxy Cholesterol

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Background

7α,25-dihydroxy Cholesterol (7α,25-DHC, 7α,25-OHC) is a potent and selective GPR183 agonist [1].
Epstein-Barr virus (EBV)-induced gene 2 (EBI2, also known as GPR183) is an orphan G protein-coupled receptor that is highly expressed in spleen and up-regulated upon Epstein–Barr-virus infection. GPR183 is required for humoral immune responses and polymorphisms in the receptor is associated with inflammatory autoimmune diseases [1][2].
7α,25-dihydroxy Cholesterol is a potent and selective GPR183 (EBI2) agonist and most potent EBI2 ligand with EC50 and Kd values of 140 pM and 450 pM, respectively. In a competition binding study, 7α,25-OHC competed for binding with IC50 value of 242 pM. In EBI2-expressing cells, 7α,25-OHC dose-dependently inhibited forskolin-induced cAMP with IC50 value of 2 nM. 7α,25-OHC was probably the endogenous ligand for EBI2. In EBI2-expressing mouse B and T cells, 7α,25-dihydroxy Cholesterol stimulated cell migration with IC50 value of around 500 pM, but had no effect on EBI2-deficient cells [1].
In EBI2-deficient mice, unseparated splenocytes, B cells and T cells were completely unresponsive to 7α,25-OHC stimulation [1]. Mice deficient in Ch25h, a key enzyme for the generation of 7α, 25-OHC, failed to position activated B cells within the spleen to the outer follicle [2].

[1]. Liu C, Yang XV, Wu J, et al. Oxysterols direct B-cell migration through EBI2. Nature. 2011 Jul 27;475(7357):519-23.
[2]. Hannedouche S, Zhang J, Yi T, et al. Oxysterols direct immune cell migration via EBI2. Nature. 2011 Jul 27;475(7357):524-7.