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.