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

We analysed IDO mRNA expression in different cell subtypes sorted from steady-state LNs. IDO mRNA was expressed to far greater levels (>5 fold) by pDCs (CD11cintPDCA-1+), than by cDCs (CD11chiPDCA-1−), B cells (CD11c−CD19+), and macrophages (CD11c−CD11b+LyC6int/+) (Fig. 1A). Consistently, IDO preferential expression by steady-state LN pDCs compared to cDCs was also observed in Balb/c mice, ruling out a mouse C57BL/6 strain restricted effect (Supplementary Fig. 1A). IDO expression by pDCs was shown to be induced by T-cell produced cytokines, such as IFN-γ and TGF-β [35], [47]. To determine whether, in steady state, T cells are involved in the regulation of IDO expression by pDCs, we measured IDO mRNA in Rag2−/− mice, which are devoid of T cells. Compared to WT mice, pDCs from steady-state LNs of Rag2−/− exhibited a significant reduction of IDO mRNA, which was in fine comparable to levels obtained in IDO−/− pDCs (Fig. 1B). We next tested whether interactions with T cell were required for IDO induction in pDCs of naïve mice. We examined IDO expression in pDCs from LNs of mice expressing a monoclonal population of CD4+ T cells specific to OVA peptide, OT-II Rag2−/− mice. IDO expression was significantly reduced and was comparable to what was seen in Rag2−/− mice (Fig. 1B). Thus, OT-II transgenic CD4+ T cells were insufficient at inducing IDO in pDCs.