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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Stephanie Oehrl - , Universität Heidelberg (Autor:in)
  • Florina Olaru - , Universität Heidelberg (Autor:in)
  • Anja Kunze - , Universität Heidelberg (Autor:in)
  • Michael Maas - , Universität Heidelberg (Autor:in)
  • Silvia Pezer - , Universität Heidelberg (Autor:in)
  • Marc Schmitz - , Institut für Immunologie, Center for Regenerative Therapies Dresden (CRTD), Nationales Centrum für Tumorerkrankungen Dresden, Universitätsklinikum Carl Gustav Carus Dresden, Deutsches Krebsforschungszentrum (DKFZ), Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Dresden (Autor:in)
  • Knut Schäkel - , Universität Heidelberg (Autor:in)

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

OriginalspracheEnglisch
Seiten (von - bis)278-284
Seitenumfang7
FachzeitschriftJournal of dermatological science
Jahrgang87
Ausgabenummer3
PublikationsstatusVeröffentlicht - Sept. 2017
Peer-Review-StatusJa

Externe IDs

PubMed 28732748

Schlagworte

Schlagwörter

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