Gasdermin D (GSDMD)-mediated pyroptosis has a significant pro-inflammation characteristic due to dramatic secretion of pro-inflammatory substances. However, its role remains unclear in psoriasis as one chronic inflammatory skin disorder with high prevalence. We found that N-terminal GSDMD (N-GSDMD) was aberrantly expressed in epidermis of skin lesion in psoriasis patients and imiquimod-induced psoriasis-like dermatitis (IIPLD) mice. In epidermis of IIPLD mice and M5 (simulating psoriatic inflammatory challenge)-treated keratinocytes cultured in vitro, cleavage products of caspase-1, GSDMD and IL-1β were increased. M5-stimulated keratinocyte presented typical pyroptosis morphology accompanied with PI-staining. Gsdmd^−/− keratinocytes could not present pyroptosis morphology while stimulated with M5. Electroporation of recombinant N-GSDMD could make the pyroptosis morphology reappear. In Gsdmd^−/− mice or keratinocyte-specific Gsdmd conditional knockout mice, we observed the alleviation of psoriatic inflammation and epidermal aberrant expression of Ki-67 and differentiation markers (loricrin and keratin 5) after imiquimod stimulation. Transplanting skin tissue from control mice to Gsdmd^−/− mice can evoke the response to imiquimod stimulation in the background of Gsdmd^−/− mice (not limited in transplanting area). In M5-stimulated keratinocytes, disulfiram or GSDMD siRNA transfection can inhibit pyroptosis and eliminate disproportionate increases of Ki-67 and PI. We further validated that topically application of disulfiram (pyroptosis inhibitor) also alleviated IIPLD in mice. These findings indicate a novel mechanism that GSDMD-mediated keratinocyte pyroptosis facilitates hyperproliferation and aberrant differentiation induced by immune microenvironment in psoriatic skin inflammation, which contributes to pathogenesis of psoriasis. Our study provides an innovative insight that targeting pyroptosis can be considered as a therapeutic strategy against psoriasis.

Fungal infections are global public health problems and can lead to substantial human morbidity and mortality. Current antifungal therapy is not satisfactory, especially for invasive, life-threatening fungal infections. Modulating the antifungal capacity of the host immune system is a feasible way to combat fungal infections. Neutrophils are key components of the innate immune system that resist fungal pathogens by releasing reticular extracellular structures called neutrophil extracellular traps (NETs). When compared with phagocytosis and oxidative burst, NETs show better capability in terms of trapping large pathogens, such as fungi. This review will summarize interactions between fungal pathogens and NETs. Molecular mechanisms of fungi-induced NETs formation and defensive strategies used by fungi are also discussed.

Introduction Accurate assessment is the basis for the effective treatment of acne vulgaris. The goal of this study was to achieve standardised diagnosis and treatment based on a deep learning model that was developed according to the current Chinese Guidelines for the Management of Acne Vulgaris. Methods The first step was to divide each image of acne vulgaris into four regions. Each of these four regions of the same patient was then combined to form a complete facial region. The second step was to classify the images based lesion type, in accordance with the current Chinese guidelines, and by treatment strategy adopted by experienced dermatologists. The final step was to evaluate the performance of the deep learning model in patients with acne vulgaris. Results The results showed that the average F1 value of the assessment model is 0.8 (optimum value = 1). The weighted kappa coefficient between the evaluation according to the artificial intelligence model and the evaluation by the attending dermatologists was 0.791 (95% confidence interval 0.671–0.910, P < 0.001), indicating a high degree of consistency. Conclusions The assessment model based on deep learning and according to the Chinese guidelines had a slightly higher overall performance is comparable to that of the attending dermatologist.

Keratinocytes, located in the outer part of human skin, are the main epidermal cell type and play an essential role in skins defense against infection. Besides creating a physical barrier between the environment and the internal body, keratinocytes exert powerful immune function in anti-pathogen infection in the skin. At the recognition stage, pattern recognition receptors (PRRs) expressed by keratinocytes sense pathogen-associated molecular patterns (PAMPs) existing in pathogens. Toll like receptors (TLRs) are the most important PRRs in keratinocytes. Other PRRs such as dectin-1 and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are also found to participate in this process. Activated PRRs enhance the secretion of cytokines, chemokines and the production of antimicrobial peptides (AMPs). Proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1α, IL-6, IL-1β and IL-18, chemokines (C-X-Cmotif) ligand (CXCL) 1, CXCL2, CCL20, CCL2 and IL-8, AMPs human β-defensin (HBD) 2, HBD3 and LL37 are the main molecules expressed in this procedure. Thymic stromal lymphopoietin (TSLP), IL-36γ, IL-17 family member IL-17C and anti-inflammatory cytokine IL-10 can also be secreted. Some molecules produced by keratinocytes such as ribonuclease 5 and 7, S100 proteins own antimicrobial properties. Keratinocytes defense responses can be regulated by internal and external factors. This review summarizes recent advances on the innate immune function of keratinocytes against infection, promoting the finding of a new direction for avoiding severe skin infection as well as the potential treatment of keratinocyte-associated inflammatory dermatosis.