Product Spotlight: Oxysterols

Posted on February 09, 2022

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Recently, Dr. William Griffiths along with his co-worker Dr. Yuqin Wang published a fascinating review of cholesterol metabolism in immunology. The review focuses on oxysterols and the past two decades of research that led to a better understanding of their relevance in human biology. For example, side-chain oxysterols and their C-7 oxidized metabolites have been proven to have a role in our immune system.

What has allowed recent research to shed new light on oxysterols and their role in the immune system?

In one word, lipidomics. Lipidomics is the work done to fully characterize molecular lipid species and their roles in biology. With advanced analytical techniques and the continued effort to standardize lipidomic analysis, quantitation and identification of lipid species in metabolic pathways has revolutionized the way we understand cholesterol metabolism and the immune system. Prior to this revolution, oxysterols were thought to simply be a part of bile acid synthesis. Now we know that oxysterols play key roles in our body’s immune response. The review article lays out a timeline of research that led to discovering the roles of 25-hydroxycholesterol (25-HC) and 7α,25-dihydroxycholesterol (25-diHC) in immune responses.

What roles do oxysterols play in the immune system?

The first major discovery related to the roles that oxysterols play in the immune response came a little over a decade ago. The study found that macrophages produced 25-HC in response to Toll-like receptor (TLR) activation. Due to this discovery, it was later determined that 25-HC is produced by macrophages is thus produced in response to viral and bacterial infections, and that it helps protect against both types of infections. 25-HC as well as its 26-HC isomer were found to be involved in the adaptive immune response as chemoattractants to immune cells.

Another fascinating discovery due to implications in autoimmune diseases is that certain oxysterols serve as ligands to RAR-related orphan receptors (RORs), specifically RORγ1 and RORγ2. ROR γ2 is expressed in various immune cells, most notably thymocytes and T helper 17 (Th17) cells. Th17 cells have been implicated in multiple sclerosis, and as such, ROR γ2 inhibitors are a target for treating autoimmune diseases.

Certain oxysterols are produced specifically in response to infection such as 25-HC and its 7-hydroxy metabolites. However, other oxysterols such as 26-HC have a constant presence under normal biological conditions. These oxysterols have similar activity to the ones produced in response to infection which may indicate that the role they play against infection is a more proactively protective role than those produced in response to infections.

It is amazing to think that just a couple decades ago oxysterols were regarded simply as a steppingstone to other biologically active molecules. With the power of advanced analytical techniques and lipidomics standards, we now know that this is not the case. Who knows what knowledge we will have about oxysterols and other lipid classes two decades from now!

Please read the full review article by Dr. Griffiths and Dr. Wang at HERE. And if you want to investigate the role of oxysterols in the immune system, check out our OxysterolSPLASH LIPIDOMIX Quantitative Mass Spec Internal Standard. This SPLASH mixture has been prepared with optimal concentrations of 13 oxysterol compounds.