Distinct oxysterol requirements for positioning naïve and activated dendritic cells in the spleen

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Science Immunology  07 Apr 2017:
Vol. 2, Issue 10, eaal5237
DOI: 10.1126/sciimmunol.aal5237

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Programming dendritic cells with cholesterol

Strategic positioning of immune cells at sites of pathogen encounter plays a critical role in mounting effective immune responses. Epstein-Barr virus–induced gene 2 (EBI2) is a G protein–coupled receptor activated by 7α,25-hydroxycholesterol (7α,25-HC) and plays an essential function in positioning naïve dendritic cells (DCs) during antigen encounter in the mouse spleen. By studying mouse strains that lack key enzymes involved in the synthesis of 7α,25-HC and related sterols, Lu et al. have found 7α,27-HC as a second physiological ligand for EBI2. Further, they show that the role of EBI2 is multitiered, as it is also employed by activated DCs to colocalize with activated helper T cells in the outer T cell zone. They also reveal factors that help shape EBI2 ligand gradients. Their studies add to our growing appreciation of how metabolites influence immune responses.