The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17 responses induced by 6-sulfo LacNAc (slan) dendritic cells

Journal of Dermatological Science
Stephanie OehrlKnut Schakel

Abstract

The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs. In vitro studies were performed analyzing the effects of apremilast on the proinflammatory function of slanDCs and their capacity to induce Th1/Th17-biased T cell responses. Increasing cAMP levels in slanDCs by PDE4 inhibition strongly reduced production of IL-12 and TNF-α. In line with these findings, co-culture experiments with apremilast-pulsed slanDCs and allogeneic T cells either from psoriasis patients or healthy controls, revealed a significant reduction of IFN-γ production and expression of the transcription factor T-bet. In parallel, production of IL-23 and IL-1ß by slanDCs was increased and co-cultured T cells revealed a largely augmented IL-17 production and an upregulated RORyt expression. We...Continue Reading

Citations

Jul 7, 2018·Frontiers in Immunology·Wojciech BaranKnut Schäkel
Mar 27, 2019·International Journal of Molecular Sciences·Adriana Rendon, Knut Schäkel
Nov 13, 2020·Frontiers in Pharmacology·Devinder ToorHridayesh Prakash
Oct 12, 2021·Frontiers in Immunology·Saradindu SahaSomdeb BoseDasgupta

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