Background: Psoriasis is a chronic inflammatory skin disease with effects that extend beyond the skin. Insulin resistance (IR) has been associated with psoriasis, but it remains unclear how indicators related to the triglyceride glucose (TyG) index, which were associate with IR, are associated with the condition.Objective: The purpose of this study was to investigate the association between psoriasis and three TyG-related indicators: triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), and triglyceride glucose-waist circumference (TyG-WC).Methods: Data from adults aged 20 to 80 years in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006 and 2009 to 2014 were utilized. Institutional Review Board approval and documented written consent was obtained from participants by NHANES (Protocol #2005–06). The patients were divided into three groups based on TyG-BMI, TyG-WC, and TyG-WHtR: Q1 (1st quintile), Q2 (2nd-3rd quintiles), and Q3 (4th-5th quintiles). Differences between the groups were further explored. Multivariate logistic regressions were used to investigate the correlation between these three indicators and psoriasis, with results expressed as odds ratios (OR) and 95% confidence intervals (CI). Subgroup analysis and supplementary analysis was further conducted to explore potential influencing factors.Results: The study included 9,291 participants, of which 260 had psoriasis. Compared Q2 and Q3 of TyG-BMI, TyG-WC, and TyG-WHtR to Q1, there were significantly associate with psoriasis. Among the three indicators, TyG-WC consistently had the highest OR values in Models 1 and 2 (Model 1: Q3 OR (95% CI) = 2.155 (1.442-3.220); Model 2: Q3 OR (95% CI) = 2.029 (1.341-3.069)). While in Model 3, the TyG-BMI shows more significant relationship with psoriasis (Model 3 of TyG-BMI: Q3 OR (95% CI) = 1.948 (1.300-3.000)). Similar results were observed in the majority of subgroups and in supplementary analysis.Conclusion: This study identified a stable and strong positive association between TyG-related indicators (TyG-BMI, TyG-WC, and TyG-WHtR) and psoriasis. This association persisted even after adjusting for multiple factors. It is suggested that high IR is significantly associated with psoriasis.

Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred treatment for AIBD involves the use of glucocorticoids or traditional immunosuppressants. Additionally, the utilization of biological agents such as rituximab, omalizumab, and dupilumab is on the rise. However, effectively managing AIBD remains a challenge. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway has been implicated in various inflammatory diseases. In recent years, a range of drugs known as JAK inhibitors, which target this pathway, have been developed. Several studies have explored the efficacy and safety of JAK inhibitors for treating AIBD. Consequently, this review begins by examining the role of the JAK/STAT pathway in AIBD, summarizing the application of different JAK inhibitors in AIBD treatment, and emphasizing the importance of disease management in treating AIBD with JAK inhibitors. Furthermore, it highlights the need for a better understanding of the JAK/STAT pathway’s role in AIBD, as well as the effectiveness and safety of JAK inhibitors for treating this disease.

Pustular psoriasis (PP) is a chronic inflammatory disease associated with multiple complications, often with hyperthermia and hypoproteinemia, and its continued progression can be life-threatening. Toll-like receptor 7 (TLR7) induces dendritic cell (DC) production of inflammatory factors that exacerbate the inflammatory response in PP. A membrane-bound chemokine expressed on DCs, CXC motif chemokine ligand 16 (CXCL16) is overexpressed in PP lesions, and neutrophils express its receptor CXC chemokine receptor 6 (CXCR6). There are few studies on the PP immune microenvironment and it is unclear whether TLR7 and CXCL16 can be used as targets in PP therapy. Skin tissue (n = 5) and blood (n = 20) samples were collected from PP and healthy normal controls. The skin tissue transcriptome was analyzed to obtain the differentially expressed genes, and the immune microenvironment was deciphered using pathway enrichment. Tissue sequencing analysis indicated that TLR7, CXCL16, DCs, and neutrophils were involved in the PP process. The enzyme-linked immunosorbent assay, reverse transcription–PCR, and scoring table results demonstrated that TLR7 induced DC secretion of CXCL16, which enabled neutrophil activation of the secretion of the inflammatory factors interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The co-culture of neutrophils with DCs treated with TLR7 inhibitor or TLR7 agonist demonstrated that TLR7 regulated neutrophil activation, migration, and apoptosis. We constructed imiquimod-induced psoriasis-like skin lesions in wild-type, Cd11c-Cre Myd88^f/f, and Mrp8-Cre Cxcr6^f/f mice. The mouse models suggested that TLR7 might influence DC release of CXCL16 and neutrophil proinflammatory effects by interfering with the myeloid differentiation primary response gene 88 (MyD88) signaling pathway. In conclusion, the TLR7–MyD88–DC–CXCL16 axis is an important mechanism that promotes neutrophil migration to PP skin lesions and stimulates the inflammatory response.

Disrupted N ⁶ -methyladenosine (m ⁶ A) modification modulates various inflammatory disorders. However, the role of m ⁶ A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m ⁶ A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m ⁶ A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m ⁶ A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m ⁶ A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m ⁶ A modification–lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m ⁶ A modulators to attenuate inflammatory skin diseases.

Background: Although there have been many epidemiological studies, research focusing on psoriasis' health burden on a global scale is still lacking. Trends and variations in the global health burden of psoriasis are evaluated by time, age, gender, geographical location, and socioeconomic status, using disability-adjusted life years (DALYs) from the Global Burden of Disease Study.Methods: The health burden of psoriasis was evaluated by DALYs, which combined years lost to disability (a morbidity component) with years of life lost (a mortality component). The global and national DALYs number, crude DALYs rate, and age-standardized DALYs rate were obtained from the GBD 2017 study database. The corresponding human development index (HDI) was collected from the United Nations Development Programme.Results: From 1990 to 2017, the DALYs number and crude DALYs rate due to psoriasis increased by 73 and 22%, respectively. In comparison, the age-standardized DALYs rate showed a slight increase. Patients in the age range of 65–69 years bear a more significant psoriasis burden. Both males and females showed an increasing trend in burden caused by psoriasis over the past 27 years, with females bearing a more significant psoriasis burden than males. The health burden of psoriasis was substantially unequal in geography with a Gini coefficient of 0.27. The concentration indexes indicated a socioeconomic associated inequality in psoriasis burden with values of 0.22, accounting for 48.64% variance across countries (R2 = 0.4864, p < 0.001). Between-nation inequality in the distribution of psoriasis burden continued to decline throughout the past 27 years. Gini coefficients of psoriasis burden decreased from 0.280 in 1990 to 0.265 in 2017. The concentration indexes indicated the same trend with 0.236 in the 1990s and 0.223 in 2017.Conclusions: Global health progress in psoriasis together with inequality in the past few decades. Although the inequality of psoriasis burden has shown some improvement during the past 27 years, disparities still exist in age, gender, geographical location, as well as socioeconomic status. The findings of this study highlight the global importance of psoriasis and is important in policy planning for psoriasis services on a global scale.

Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of how phospholipase PLA2G4B mediates local immune dysfunction and skin lesions remains unclear. The aim of this study was to explore the mechanisms of anti-psoriasis and immune suppression effect by inhibiting PLA2G4B in psoriasis progression. We successfully transfected si-PLA2G4B in a murine keratinocyte cell-line PAM212 to verify the effect of progression by PLA2G4B. The Imiquimod psoriasis mouse model was then successfully constructed, followed by emulsion wrapped PLA2G4B-siRNA applied to the skin lesions. The phenotype, pathology, immunofluorescence staining of PLA2G4B, IL17, CD3, and CD1b, and bulk transcriptome analysis were performed to decipher the effect and mechanism of si-PLA2G4B. Interfering with PLA2G4B significantly inhibited the proliferation and migration of PAM212. The interference of PLA2G4B in vivo showed a therapeutic effect on psoriasis, comparable to that of betamethasone. The phenotype and pathology revealed reduced keratinocytes in the si-PLA2G4B group compared to the model mice. Immunofluorescence showed that CD1b, CD3+ T cells, and IL17 were suppressed in the skin lesions. RNA-seq and deconvolution revealed that immune cells such as myeloid dendritic cell and T cell CD8+ naive were inactivated. Th17 reduce the release of inflammatory factors such as IL17 and IL36. Pathway analysis revealed the potential therapeutic mechanism involved in the inhibition of sphingolipid or ceramide secretion. This study verified the anti-psoriatic effect of using si-PLA2G4B. The immune response was alleviated after administration. This phospholipase inhibition-based therapy sheds light on the pharmaceutical potential against psoriasis.