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

Plasmacytoid dendritic cells (pDCs) are important sensors of non-self-nucleic acids derived from bacteria or viruses and are crucial mediators of innate anti-microbial responses through the production of inflammatory cytokines and type-I IFNs [1], [2]. In addition, pDCs have been implicated in the development of several autoimmune diseases, including lupus, psoriasis, multiple sclerosis (MS) and type-1 diabetes [3], [4], [5], [6], [7]. Following abnormal release of self-DNA during inflammatory processes, pDCs are activated through TLR signalling and subsequently produce type-I IFN [8]. Importantly, a few years ago, the notion emerged that pDCs act not only as innate sensors but can also function as bona fide antigen (Ag) presenting cells (APCs) and directly impact T cell responses [9]. It was shown that pDCs capture and process Ags [10], and load antigenic peptides onto MHC class I (MHCI) [11] and MHC class II (MHCII) molecules [12], [13], [14]. The modulation of Ag-presenting pDC functions led to important consequences on T cell immunity, the outcome being highly dependent on the cytokine microenvironment [15].