Activation of type I IFN axis in oral cGVHD. (A) IL-15 expression in the keratinocytes and infiltrating cells in a patient with severe oral cGVHD. (B) Patient without oral cGVHD. (C) Negative isotype staining control. IL-15 mRNA (mean ± SEM) is increased in severe oral GVHD (n = 6) compared with mild cGVHD (n = 10) or controls (n = 5) and correlates with that of T-bet (D-E). Increased expression of MxA, IFN α/β–inducible protein, in oral cGVHD. (F) Patient with severe disease. (G) Control patient lacking oral cGVHD. (H) Negative isotype staining control. (I) MxA (MPI ± SEM) is markedly up-regulated in patients with severe oral cGVHD (n = 9) compared with those with mild disease (n = 7) or control patients (n = 6). MxA expression in the affected tissues correlates with the number of infiltrating T cells, assessed as CD3⁺ cells/HPF (J). STAT1 phosphorylation and nuclear translocation is observed in the patients with severe cGVHD (K), but not control patients (L). (M) Negative isotype staining control. (N) Plasmacytoid dendritic cells identified by expression of CD2ap in the patient with severe oral cGVHD and high type I IFN activity as measured by MxA expression. (O) Close-up of the image in panel N, showing coexpression of CD2ap and CD68 in a granular peripheral pattern. (P) No CD2ap-expressing cells and few CD68 cells are present in the mucosa of a patient without oral cGVHD. (Q) Negative control. AU indicates arbitrary units; MPI, mean pixel intensity.