Migratory and not lymphoid-resident dendritic cells maintain peripheral self-tolerance and prevent Autoimmunity via induction of iTreg cells

There is evidence that dendritic cells (DCs) induce peripheral tolerance. Nevertheless, it is not known whether immature DCs in general are able to tolerize CD4+ T cells or if this is a prerogative of specialized subtypes. Here, we show that, when autoantigen presentation is extended to all conventional mouse DCs, immature lymphoid tissue resident DCs are unable to tolerize CD4+ T cells. In contrast, this is a prerogative of steady state migratory DCs. The way they contribute to tolerance development is via the induction of autoantigen-specific regulatory T (iTreg) cell conversion. Since only lymph nodes host migratory DCs, iTreg cells develop solely in lymphnodes, and not in the spleen, and are retained inside the lymph nodes.Mechanistically, in cutaneous lymph nodes, DC-derived CCL22contributes to the retention of iTreg cells. The importance of the local generation of iTreg cells is emphasized by their essential role in preventing autoimmunity.