Dendritic cell differentiation in the presence of PGE2 primes dendritic cells for a proinflammatory response, induces IL‐23, and promotes Th17 differentiation

Dendritic cells (DC) play an important role in the induction of the immune responses. The DC phenotype and function is modified by different factors. PGE2 plays an important role in inflammation and autoimmunity through changes in the proinflammatory cytokine profile. The proinflammatory cytokine IL‐23 is associated with autoimmune disorders. In the periphery, macrophages and DC are major producers of IL‐23, whereas microglia play a similar role in the CNS. IL12 and IL‐23 share the p40 subunit, but have specific p35 (IL‐12) and p19 (IL‐23) subunits. The main goal of this study was to define the role of PGE2 in DC differentiation and production of bioactive IL‐23. DC were generated in GM‐CSF (DC) or GM‐CSF+PGE2 (DCp) and characterized following stimulation with LPS. PGE2 functions as an enhancer of DC differentiation and influence their Th‐cells lineage driving ability, by providing factors required for Th17 differentiation and survival. Activated DCp have higher levels of proinflammatory cytokines, such as IL‐6, IL‐1β and TNF, as a result of higher levels of TLR expression and of NFkBp65 phosphorylation and nuclear translocation. In addition, PGE2 shifts the IL‐23/IL‐12 balance in favor of IL‐23 in activated DC. These observations may help to understand the distinct role of PGE2 in the induction of pathogenic Th17‐cells. This work is support by NIH/NIAID R01AI052306