NF-κB1 Contributes to Imiquimod-Induced Psoriasis-Like Skin Inflammation by Inducing Vγ4+Vδ4+γδT17 Cells

Recent studies have identified NF-kappa B1 as a new disease susceptibility gene for psoriasis. Although accumulating evidence has shown the importance of NF-kappa B signaling in various cell types in the pathogenesis of psoriasis, it remains unclear how NF-kappa B1 contributes to the pathogenesis of psoriasis. In this study, we examined psoriasis-like skin diseases induced by topical administration of imiquimod in Nf-kappa b1-deficient (Nf-kappa b1(-/-)) mice and littermate wild-type (WT) mice. Compared with WT mice, Nf-kappa b1(-/-) mice exhibited attenuated skin inflammation. The numbers of V delta 4(+)V delta 4(+)gamma delta T17 cells, which cause skin inflammation in this model, were significantly reduced in the skin and draining lymph nodes in imiquimod-treated Nf-kappa b1(-/-) mice. Nf-kappa b1 is preferentially phosphorylated in V delta 4(+)V delta 4(+)gamma delta T17 cells in WT mice. In vitro proliferation of V delta 4(+)V delta 4(+)gamma delta T17 cells but not conventional CD4(+) T cells was significantly impaired in Nf-kappa b1(-/-) mice compared with that in WT mice. RNA-sequencing analyses revealed that the expression of E2 factor target genes was decreased in V delta 4(+)V delta 4(+)gamma delta T cells by the absence of NF-kappa B1. Consistently, the cell cycle progression of V delta 4(+)V delta 4(+)gamma delta T cells was reduced in Nf-kappa b1(-/-) mice compared with that in WT mice. These results suggest that Nf-kappa b1 plays a crucial role in the pathogenesis of imiquimod-induced psoriasis-like skin inflammation by promoting the proliferation of V delta 4(+)V delta 4(+)gamma delta T17 cells.