Editorial: 25-Hydroxycholesterol: a new life in immunology

Abstract

A discussion on paper by Park and Scott revealing the signaling pathways leading to the synthesis of a potent immunoregulatory oxysterol by macrophage and dendritic cells.

Figure 1.. Signaling pathways in macrophages and DCs leading to the induction of cholesterol 25-hydroxylase and the reactions catalyzed by this enzyme.

(A) TLR ligands activate cell surface and intracellular receptors that signal through several adapters leading to the expression of IFN-β. The binding of this cytokine to the IFNR activates a transcription factor cascade, which in turn, induces the cholesterol 25-hydroxylase gene. The product of this gene is an enzyme of the ER that produces 25-hydroxycholesterol by the reaction shown in B. 25-Hydroxycholesterol is metabolized further to a 7α-hydroxylated sterol by the CYP7B1 oxysterol 7α-hydroxylase. Question marks denote steps in the signaling pathways that have not yet been confirmed by direct experimental evidence; these steps include the role of TLR4 in signaling from an intracellular compartment and the direct involvements of phosphorylated (p)STAT1 and NF-κB in expression of the cholesterol 25-hydroxylase gene.