Increased plasmacytoid dendritic cells and RORγt-expressing immune effectors in cutaneous acute graft-versus-host disease

Evidence for a role of plasmacytoid dendritic cells and Th17 mediated responses in human cutaneous acute GVHD. The role of PDCs and Th17 cells is not well understood in the pathogenesis of aGVHD. We evaluated PDC and Th17 cells in skin biopsies of 38 patients at diagnosis of aGVHD. The biopsies were tested by immunohistochemistry for the expression of BDCA2, a typical marker of PDCs. We found an increase of BDCA2(+) cells in the skin of the patients with aGVHD. Moreover, we observed a strong expression of the type I IFN-inducible protein Mx1 in the skin of the patients with aGVHD, compared with that of those without it, suggesting that PDCs produce type I IFN. We also analyzed the expression of two Th17 surface markersCD161 and CCR6and RORt, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of RORt(+), CD161(+), and CCR6(+) cells were counted in the skin of the patients with aGVHD than in the skin of those who underwent allo-SCT and in whom aGVHD did not develop. This study provides evidence for a role of Th17-mediated responses and a potential new pathophysiological link between PDCs and Th17 in human cutaneous aGVHD.