TRIM21is important in the early phase of inflammation in the imiquimod-induced psoriasis-like skin inflammation mode

Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood.We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new early biological events in psoriasis after adalimumab treatment, which may reflect decreased attraction of immune cells by downregulation of first chemokines and then their ligands (IL-8, CXCL9 and CXCL10 after 4 days of treatment; and IL8RB and CXCR-4 after 14 days). We also found downregulation of angiogenesis by downregulation of chemokines like CCL19 and CCL21 after 4 days of treatment and downregulation of VEGFA after 14 days.Combining microarray data on biopsies from psoriasis patients with pathway analysis allows us to integrate earlier in vitro findings into the identification of mechanisms that may be important in vivo.