title: PGI₂ signaling inhibits antigen uptake and increases migration of immature dendritic cells.
abstract: PGI₂ signaling through IP inhibits allergen-induced inflammatory responses in mice. We reported previously that PGI₂ analogs decreased proinflammatory cytokine and chemokine production by mature BMDCs. However, whether PGI₂ modulates the function of immature DCs has not been investigated. We hypothesized that PGI2 negatively regulates immature DC function and investigated the effect of PGI2 analogs on immature BMDC antigen uptake and migration in vitro and in vivo. Immature BMDCs were obtained from WT and IPKO mice, both on a C57BL/6 background. The PGI2 analog cicaprost decreased FITC-OVA uptake by immature BMDCs. In addition, cicaprost increased immature BMDC podosome dissolution, pro-MMP-9 production, cell surface CCR7 expression, and chemotactic migration toward CCL19 and CCL21, as well as chemokinesis, in an IP-specific fashion. These in vitro results suggested that cicaprost promotes migration of immature DCs from mucosal surface to draining LNs. This concept was supported by the finding that migration of immature GFP⁺ BMDCs to draining LNs was enhanced by pretreatment with cicaprost. Further, migration of immature lung DCs labeled with PKH26 was enhanced by intranasal cicaprost administration. Our results suggest PGI2-IP signaling increases immature DC migration to the draining LNs and may represent a novel mechanism by which this eicosanoid inhibits immune responses.
authors.affiliation: Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, 1161 21st Ave., T-1218 MCN, Nashville, TN 37232-2650, USA. shinji.toki@vanderbilt.edu
authors.forename: Shinji
authors.initials: S
authors.lastname: Toki
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Huckabee
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Newcomb
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
authors.forename: William E
authors.initials: WE
authors.lastname: Lawson
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D054415:Chemokine CCL19 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000378:metabolism; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D054400:Receptors, CCR7 / Q000378:metabolism; D044006:Receptors, Epoprostenol / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D054400:Receptors, CCR7; D044006:Receptors, Epoprostenol; D010047:Ovalbumin; D011464:Epoprostenol
keywords: CCR7; chemotaxis; lymph node; podosome