title: Membrane-bound metallothionein 1 of murine dendritic cells promotes the expansion of regulatory T cells in vitro.
abstract: Exposure to environmental toxicants can alter a range of cellular functions involved in the immune response. Increased expression of the stress protein metallothionein 1 (MT1) is one example hereof. Previously, it has been reported that MT1 has several immunosuppressive properties. Furthermore, we earlier showed that functionally tolerogenic dendritic cells (DCs) expressed increased mRNA levels of MT1. Here, we demonstrate that dexamethasone-treated murine DCs are functionally tolerogenic and produce MT1. However, these DCs do not actively transport MT1 to the cell membrane and their regulatory function does not depend on MT1. Alternatively, ZnCl2-treated murine DCs transport MT1 to the cell surface are tolerogenic and promote the expansion of T cells with a regulatory phenotype. Moreover, the membrane-bound MT1 was shown to be essential for ZnCl2-treated DCs to exert their regulatory function. On the basis of this, MT1 can be used as a new marker for functionally tolerogenic DCs. Additionally, we have found a new mechanism for tolerogenic DCs to exert their immune regulatory function.
authors.affiliation: Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.
authors.forename: Rachel
authors.initials: R
authors.lastname: Spiering
authors.forename: Josée
authors.initials: J
authors.lastname: Wagenaar-Hilbers
authors.forename: Veerle
authors.initials: V
authors.lastname: Huijgen
authors.forename: Ruurd
authors.initials: R
authors.lastname: van der Zee
authors.forename: Peter J S
authors.initials: PJ
authors.lastname: van Kooten
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Femke
authors.initials: F
authors.lastname: Broere
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D002712:Chlorides; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D017967:Zinc Compounds; C525355:metallothionein-1, mouse; D003907:Dexamethasone; C016837:zinc chloride; D008668:Metallothionein
keywords: dendritic cells; immune regulation.; metallothionein 1; stress protein