title: EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture.
abstract: Splenic dendritic cells (DCs) present blood-borne antigens to lymphocytes to promote T cell and antibody responses. The cues involved in positioning DCs in areas of antigen exposure in the spleen are undefined. Here we show that CD4(+) DCs highly express EBI2 and migrate to its oxysterol ligand, 7α,25-OHC. In mice lacking EBI2 or the enzymes needed for generating normal distributions of 7α,25-OHC, CD4(+) DCs are reduced in frequency and the remaining cells fail to situate in marginal zone bridging channels. The CD4(+) DC deficiency can be rescued by LTβR agonism. EBI2-mediated positioning in bridging channels promotes DC encounter with blood-borne particulate antigen. Upon exposure to antigen, CD4(+) DCs move rapidly to the T-B zone interface and promote induction of helper T cell and antibody responses. These findings establish an essential role for EBI2 in CD4(+) DC positioning and homeostasis and in facilitating capture and presentation of blood-borne particulate antigens. DOI:http://dx.doi.org/10.7554/eLife.00757.001.
authors.affiliation: Department of Microbiology and Immunology , University of California, San Francisco , San Francisco , United States ; Howard Hughes Medical Institute, University of California, San Francisco , San Francisco , United States.
authors.forename: Tangsheng
authors.initials: T
authors.lastname: Yi
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology*; D006706:Homeostasis; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology*
chemical_list: D000941:Antigens; C543809:Gpr183 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: Dendritic cells; EBI2; Mouse; Oxysterols; antigen capture; lymphotoxin; spleen bridging channel