Controlling the pro-inflammatory function of 6-sulfo LacNAc (slan) dendritic cells with dimethylfumarate

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Stephanie Oehrl - , Heidelberg University  (Author)
  • Florina Olaru - , Heidelberg University  (Author)
  • Anja Kunze - , Heidelberg University  (Author)
  • Michael Maas - , Heidelberg University  (Author)
  • Silvia Pezer - , Heidelberg University  (Author)
  • Marc Schmitz - , Institute for Immunology, Center for Regenerative Therapies Dresden, National Center for Tumor Diseases Dresden, University Hospital Carl Gustav Carus Dresden, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK) Partner Site Dresden (Author)
  • Knut Schäkel - , Heidelberg University  (Author)

Abstract

Backround The fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1 T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS. Objective To explore the influence of DMF on functional properties and cell signaling pathways of slanDCs. Methods In the context of slanDCs we studied the role of DMF in modulating cell migration, phenotypic maturation, cytokine production, cell signaling and T cell stimulation. Results Initially, we observed the reduction of slanDCs numbers in psoriasis skin lesions of FAE treated patients. Studying whether DMF controls the migratory capacity of slanDCs to chemotactic factors expressed in psoriasis we observed an inhibition of the CX3CL1 and C5a depedent cell migration. DMF also attenuated the rapid spontaneous phenotypic maturation of slanDCs, as judged by a reduced CD80, CD86, CD83 and HLA-DR expression. In addition, we observed a DMF-dependent decrease of IL-23, IL-12, TNF-α and IL-10 secretion, and noticed a reduced capacity to stimulate Th17/Th1 responses. DMF targeted in slanDCs different intracellular cell signaling pathways including NFκB, STAT1 and HO-1. Conclusions With this study we identify a frequent pro-inflammatory cell type found in psoriasis and MS as a relevant target for the therapeutic immunomodulatory effects of DMF.

Details

Original languageEnglish
Pages (from-to)278-284
Number of pages7
JournalJournal of dermatological science
Volume87
Issue number3
Publication statusPublished - Sept 2017
Peer-reviewedYes

External IDs

PubMed 28732748

Keywords

Keywords

  • Cell migration, Dendritic cells, Dimethylfumarate, Psoriasis, slanDCs