Still waters run deep: latent cytokine activity in nonlesional psoriasis skin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116968/1/bjd14248_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116968/2/bjd14248.pd

Early tissue responses in psoriasis to the antitumour necrosis factor‐α biologic etanercept suggest reduced interleukin‐17 receptor expression and signalling

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108076/1/bjd12937-sup-0005-TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108076/2/bjd12937-sup-0004-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108076/3/bjd12937.pd

Cutaneous manifestations of hospitalized coronavirus disease 2019 patients: a report of six cases with clinicopathologic features and viral RNA in situ hybridization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163863/1/jdv16741.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163863/2/jdv16741_am.pd

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27–mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus

Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10−89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton’s tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS