A carbamazepine metabolite activates NLRP3 and controls skin homing of CD8 T-cells in SJS/TEN.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions with extensive keratinocyte death. Carbamazepine (CBZ), the most commonly implicated drug in SJS/TEN, is metabolized by the cytochrome P450 enzyme 3A4 (CYP3A4) into carbamazepine-10,11-epoxide (CBZE) in the liver. While CD8 cytotoxic T cells play an important role in SJS/TEN, the underlying mechanism of exuberant immune response by CD8 T cells in these conditions remains incompletely understood.

Eosinophil extracellular traps drive T follicular helper cell differentiation via VIRMA-dependent MAF stabilization in bullous pemphigoid.

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the presence of pathogenic autoantibodies and a substantial influx of immune cells into skin lesions. However, the role of eosinophils in BP remains inadequately elucidated.

Objective: We sought to determine the pathologic involvement of eosinophils and eosinophil extracellular traps (EETs) in BP.

CREB1-driven CXCR4 neutrophils promote skin inflammation in mouse models and human patients.

Neutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4 neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity.

Assessment of relationships between bullous pemphigoid and neurological diseases: A bidirectional two-sample Mendelian randomization study.

Bullous pemphigoid (BP) is the most prevalent autoimmune vesiculobullous skin illness that tends to affect the elderly. Growing evidence has hinted a correlation between BP and neurological diseases. However, existing observational studies contained inconsistent results, and the causality and direction of their relationship remain poorly understood.

CXCL12/CXCR4 Axis Drives the Chemotaxis and Differentiation of B Cells in Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by autoantibodies against the hemidesmosomal proteins in the skin and mucous membranes. The efficiency of B-cell‒targeting biologics in BP indicates the important role of B cells in its pathogenesis. However, abnormal B-cell migration and differentiation in BP require further elucidation.

EZH2-dependent epigenetic modulation of histone H3 lysine-27 contributes to psoriasis by promoting keratinocyte proliferation.

Psoriasis is characterized by keratinocyte hyperproliferation. While significant progress has been made in understanding the molecular mechanism regulating the proliferation of keratinocytes, little is known about the epigenetic factors that control this process. EZH2 and EZH2 mediated trimethylation of histone H3 lysine 27 (H3K27me3) was previously shown ectopically expressed in carcinoma and mediated proliferation, thereby we sought to clarify the role of EZH2-H3K27me3 in the proliferation of psoriatic keratinocyte.

Comparative effectiveness of different therapies for treating striae distensae: A systematic review and network meta-analysis.

Background: Striae distensae (SD) are common and aesthetically undesirable dermal lesions. The aim of this study is to comprehensively evaluate the effectiveness of different therapies in treating striae distensae using network meta-analysis.

Methods: A systematic search of electronic databases up to December 1, 2019 was conducted.

Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk.

Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through activation of epidermal TLR4/IL-36R crosstalk. This activation is dependent upon NETs formation and integrity, as targeting NETs with DNase I or CI-amidine improves disease in the imiquimod (IMQ)-induced psoriasis-like mouse model, decreasing IL-17A, lipocalin2 (LCN2), and IL-36G expression.

Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production.

Psoriasis is a chronic inflammatory autoimmune skin disease that often occurs in rubbed areas undergoing a strong mechanical stretch, such as the elbows and knees. However, the pathologic role of mechanical tension in psoriasis remains unclear. In this study, we investigated the contribution of keratinocyte mechanical stretch to the clinical features of psoriasis.

Identification of Immunodominant Th2-Cell Epitopes in Chinese Patients with Bullous Pemphigoid.

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease caused by autoantibodies targeting the juxtamembranous extracellular noncollagenous 16A (NC16A) domain of human collagen XVII (also known as BP180). Because T-helper (Th) cells are essential for antibody responses to antigens, we adopted an assay to map the immunodominant Th2-cell epitopes in NC16A. We synthesized 22 overlapping peptides spanning the entire sequence of BP180-NC16A and investigated the reactivity of Th2 cells from patients with BP to these peptides using the Enzyme-Linked ImmunoSpot (ELISPOT) assay.

Proinflammatory role of blister fluid-derived exosomes in bullous pemphigoid.

Bullous pemphigoid is an autoimmune inflammatory disorder characterized by the presence of autoantibodies against bullous pemphigoid autoantigens, leading to dermal-epidermal separation with consequent blister formation. However, whether and how the components of blister fluid exacerbate the progression of bullous pemphigoid is unclear. Exosomes are nanometre-sized vesicles released from cells into the body fluid, where they can transmit signals throughout the body.

Association of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans.

Background: Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease.

Objectives: To evaluate the association of HLA class I and HLA class II alleles with susceptibility to BP in the northern Chinese Han population.

Semaphorin 4D from CD15 Granulocytes via ADAM10-Induced Cleavage Contributes to Antibody Production in Bullous Pemphigoid.

Autoreactive B-cell activation and antibody production are critical events for the development of bullous pemphigoid (BP). However, the mechanism that is involved in the modulation of B-cell activation and autoantibody generation has not been fully understood. Semaphorin 4D (Sema4D, or CD100) plays important roles in immune regulation related to B cells, but its implications in BP remain obscure.

Decreased expression levels of complement regulator CD55 contribute to the development of bullous pemphigoid.

Bullous pemphigoid is a common autoimmune blistering disease of the elderly associated with autoantibody-mediated complement activation, and complement dysregulation is critical for its pathogenesis. As a crucial regulator of the complement system, CD55 has been widely studied in autoimmune diseases. Here, we investigated the involvement of CD55 in bullous pemphigoid, as little is known regarding its role in this disease.

Semaphorin4D Drives CD8 T-Cell Lesional Trafficking in Oral Lichen Planus via CXCL9/CXCL10 Upregulations in Oral Keratinocytes.

Chemokine-mediated CD8 T-cell recruitment is an essential but not well-established event for the persistence of oral lichen planus (OLP). Semaphorin 4D (Sema4D)/CD100 is implicated in immune dysfunction, chemokine modulation, and cell migration, which are critical aspects for OLP progression, but its implication in OLP pathogenesis has not been determined. In this study, we sought to explicate the effect of Sema4D on human oral keratinocytes and its capacity to drive CD8 T-cell lesional trafficking via chemokine modulation.