Dendritic Cells and Macrophages in the Pathogenesis of Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. This disease impairs patients' quality of life enormously. Pathological findings demonstrate proliferation and abnormal differentiation of keratinocytes and massive infiltration of inflammatory immune cells. The pathogenesis of psoriasis is complicated. Among immune cells, dendritic cells play a pivotal role in the development of psoriasis in both the initiation and the maintenance phases. In addition, it has been indicated that macrophages contribute to the pathogenesis of psoriasis especially in the initiation phase, although studies on macrophages are limited. In this article, we review the roles of dendritic cells and macrophages in the pathogenesis of psoriasis.

Transcriptional programming of immunoregulatory responses in human Langerhans cells.

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.