Psoriasis
Neutrophil Extracellular Traps Induce Human Th17 Cells: Effect of Psoriasis-Associated TRAF3IP2 Genotype
Psoriasis lesions are rich in IL-17–producing T cells as well as neutrophils, which release webs of DNA-protein complexes known as neutrophil extracellular traps (NETs). Because we and others have observed increased NETosis in psoriatic lesions, we hypothesized that NETs contribute to increased T helper type 17 (Th17) cells in psoriasis. After stimulating peripheral blood mononuclear cells with anti-CD3/CD28 beads for 7 days, we found significantly higher percentages of CD3+CD4+IL-17+ (Th17) cells in the presence versus absence of NETs, as assessed by flow cytometry, IL-17 ELISA, and IL17A/F and RORC mRNAs.The Genetics of Chronic Itch: Gene Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch
To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and nonitchy, nonlesional skin biopsies from 25 patients with atopic dermatitis and 25 patients with psoriasis and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared with healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and nonitchy skin in atopic and psoriatic subjects.IL-17 Responses Are the Dominant Inflammatory Signal Linking Inverse, Erythrodermic, and Chronic Plaque Psoriasis
Inverse and erythrodermic psoriasis are rare subtypes of psoriasis. Whereas the former is characterized by shiny erythematous nonscaly plaques in the body folds, the latter has widespread redness with fine scale, covering over 80% of the body surface area, and can be life threatening. Both are clinical subtypes of chronic plaque psoriasis and often coexist or evolve from plaque psoriasis (Boyd and Menter, 1989; Omland and Gniadecki, 2015), but the pathogenic mechanisms involved are unknown, and current treatments are frequently unsatisfactory (Rosenbach et al., 2010).Cross-Disease Transcriptomics: Unique IL-17A Signaling in Psoriasis Lesions and an Autoimmune PBMC Signature
Transcriptome studies of psoriasis have identified robust changes in mRNA expression through large-scale analysis of patient cohorts. These studies, however, have analyzed all mRNA changes in aggregate, without distinguishing between disease-specific and nonspecific differentially expressed genes (DEGs). In this study, RNA-seq meta-analysis was used to identify (1) psoriasis-specific DEGs altered in few diseases besides psoriasis and (2) nonspecific DEGs similarly altered in many other skin conditions.The Spectrum of Mild to Severe Psoriasis Vulgaris Is Defined by a Common Activation of IL-17 Pathway Genes, but with Key Differences in Immune Regulatory Genes
Mild versus severe psoriasis is often distinguished by clinical measures such as the extent of skin involvement or Psoriasis Area and Severity Index score, both of which use arbitrary boundaries. It is widely assumed that severe psoriasis involves higher levels of skin inflammation, but comparative molecular profiles of mild versus severe disease have not been performed. In this study, we used immunohistochemistry, reverse transcription PCR, and gene arrays to determine the phenotype of North American patients with mild psoriasis (n = 34, mean PASI score = 5.5) versus severe psoriasis (n = 23, mean PASI score = 23.2).
