PGI₂ signaling inhibits antigen uptake and increases migration of immature dendritic cells.

Toki S, Goleniewska K, Huckabee MM, Zhou W, Newcomb DC, Fitzgerald GA, Lawson WE, Peebles RS
J Leukoc Biol. 2013 94 (1): 77-88

PMID: 23625201 · PMCID: PMC3685021 · DOI:10.1189/jlb.1112559

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.

MeSH Terms (20)

Animals Bone Marrow Cells Cell Movement Chemokine CCL19 Chemokine CCL21 Chemotaxis Cytokines Dendritic Cells Epoprostenol Female Flow Cytometry Male Mice Mice, Inbred C57BL Mice, Knockout Ovalbumin Platelet Aggregation Inhibitors Receptors, CCR7 Receptors, Epoprostenol Signal Transduction

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