IL-4 and IL-13 Alter Plasmacytoid Dendritic Cell Responsiveness to CpG DNA and Herpes Simplex Virus-1

Human plasmacytoid dendritic cells (pDCs) are found in skin lesions in a wide variety of diseases. The role of the microenvironment in these lesions on the function of human pDCs remains elusive. We sought to determine the effect of Th2 cytokines on the ability of human pDCs to respond to CpG oligodeoxynucleotides (ODNs) and herpes simplex virus in vitro. In this study, we found that the Th2 cytokines, IL-4 and IL-13, modulate Toll-like receptor 9 (TLR-9)- and herpes simplex virus-induced pDC phenotype and enhance the ability of these cells to induce allogeneic T-cell responses. Moreover, Th2 cytokines impaired TLR-9-induced secretion of inflammatory cytokines and chemokines. Taken together, these results demonstrate that Th2 cytokines are involved in the modulation of pDC function and responsiveness to bacterial- and viral-derived stimuli.