Innate Signaling of HPV 6/11-infected Keratinocytes Modulates the Immune Response in RRP. Keratinocytes harboring persistent HPV-infection have increased levels of PGE2 and CCL20, while levels of the pro-inflammatory cytokine IL-36 γ are decreased. The alterations in this cytokine milieu inhibit the normal activation of Langerhans cells, which in turn reduces the number of HPV-specific TH1 cells in the lesion and supports regulatory T-cell differentiation from TH0 T-cells. In addition, the localized polarization of T cells toward a TH2 phenotype reduces the TH1 population in the lesion. Lack of HPV-specific TH1 cells, results in low levels of HPV-specific CD8+ cells that supports a micromilieu of immune suppressive cells, chemokine, and cytokines that supports persistent HPV infection.