IDO-orchestrated crosstalk between pDCs and Tregs inhibits autoimmunity

Lippens, Carla; Duraes, Fernanda V.; Dubrot, Juan; Brighouse, Dale; Lacroix, Mathilde; Irla, Magali; Aubry-Lachainaye, Jean-Pierre; Reith, Walter; Mandl, Judith N.; Hugues, Stéphanie

Many studies, including those investigating oral tolerance and allograft models, suggest that steady-state Ag-presenting pDCs exclusively promote T cell tolerance [16], [17], [18]. Although the nature of the factors controlling distinct pDC functions remains to be established, once activated, pDCs exhibit both immunogenic and tolerogenic functions. For example, using mice exhibiting a specific loss of MHCII expression by pDCs, we showed that CpG-B activated pDCs present Ag and promote effector Th17 cell differentiation, a property that can be exploited for anti-tumor vaccines [19]. Pro-pathogenic Ag-presenting pDCs were similarly described in a mouse model of atherosclerosis in which pDCs induced pathogenic Th1 cells [20]. In addition, BST-2 mediated specific Ag delivery to CpG-activated pDCs led to cytotoxic T lymphocyte (CTL) and Th1 cell differentiation and triggered protective immunity against viral infection and tumor growth [21]. In contrast, in the context of EAE, Ag targeting to pDCs via Siglec-H promoted CD4+ T cell anergy and inhibited CNS inflammation [22]. We previously demonstrated that in EAE, pDCs present myelin Ags on MHCII molecules to induce the expansion of suppressive Tregs, a phenomenon correlated with disease amelioration [23].