Staphylococcus aureus (S aureus) commonly causes skin infections and is abundant on the skin of patients with atopic dermatitis, where it worsens inflammation and drives skin barrier defects. Neutrophils help to control...Staphylococcus aureus (S aureus) commonly causes skin infections and is abundant on the skin of patients with atopic dermatitis, where it worsens inflammation and drives skin barrier defects. Neutrophils help to control S aureus infection through their antimicrobial activity and by recruiting other immune cells; however, they can also promote S aureus skin colonization. Excessive neutrophil activity and release of neutrophil extracellular traps may impair the skin barrier and thereby promote colonization. Moreover, S aureus has evolved strategies to evade neutrophil defenses. This review explores neutrophil-skin interactions in healthy and inflamed skin and potential therapeutic strategies targeting these interactions to reduce S aureus colonization in diseases like atopic dermatitis.
Skin bleaching is a global practice driven by intersecting historical, cultural, psychological, and economic influences that equate lighter skin with beauty, status, and opportunity. Its prevalence remains high among ski...Skin bleaching is a global practice driven by intersecting historical, cultural, psychological, and economic influences that equate lighter skin with beauty, status, and opportunity. Its prevalence remains high among skin-of-color populations globally. Traditional agents, such as hydroquinone, mercury, and corticosteroids, persist alongside newer agents and medicalized regimens with oral and injectable agents. Associated complications span dermatologic, systemic, and psychosocial domains, constituting the emerging skin bleaching phenomenon. Despite regulatory restrictions, enforcement remains inconsistent. This narrative review examines the global epidemiology, evolving demographics, complications, and regulatory landscapes and outlines collaborative clinical, public health, regulatory, and sociocultural strategies to address this persistent global health concern.
Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the production of autoantibodies; however, the molecular mechanisms regulating plasma cell differentiation remain unclear. This study investiga...Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the production of autoantibodies; however, the molecular mechanisms regulating plasma cell differentiation remain unclear. This study investigated the role of plasma-derived extracellular vesicles (EVs) and their microRNA cargo in regulating this process. EVs isolated from patients with BP and healthy controls were functionally assessed. BP-derived EVs significantly enhanced plasmablast differentiation, increased pathogenic autoantibody production, and elevated IL-6 secretion. High-throughput sequencing identified miR-148a-3p as a selectively enriched and functionally critical microRNA within BP EVs. Mechanistically, miR-148a-3p promoted plasmablast differentiation by targeting the BACH2/mTOR signaling pathway. This was validated using dual-luciferase reporter assays, western blotting, RT-qPCR, and flow cytometry. These findings reveal, to our knowledge, a previously unrecognized EV-mediated regulatory mechanism in BP pathogenesis and identify miR-148a-3p as a potential diagnostic biomarker and therapeutic target.
Peters RHW, Smits JPH, van den Bogaard EH
… +11 more, Kelemen E, Krohn IK, De Vriese S, Gutowska-Owsiak D, Sevilla LM, Pérez P, Furundžić D, Hedtrich S, Zalewska-Janowska A, Simon M, Dubrac S
Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by an aberrant T helper 2 immune response and impaired epidermal barrier function, regardless of phenotypes and endotypes. Historically,...Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by an aberrant T helper 2 immune response and impaired epidermal barrier function, regardless of phenotypes and endotypes. Historically, AD has been extensively studied in mouse models, which have intrinsic limitations, notably in the translatability of results to patients. Moreover, ethical concerns have driven the field toward the development of organotypic AD skin models. The recent steep increase in their use warrants an expert opinion on the advantages and limitations of such models and opportunities for their improvement, which are presented in this paper.
Han J, Lisco A, Che Y
… +15 more, Anderson MV, Laidlaw E, Kim CS, Hou P, Conlan S, Proctor DM, Lee-Lin S, Amirkhani A, Holmes CJ, Suh GS, Brownell I, NISC Comparative Sequencing Program, Segre JA, Sereti I, Kong HH
The microbiome and host immune system maintain a dynamic homeostatic equilibrium at the skin interface. Prior studies have shown that the skin microbiome is profoundly altered in immunodeficient conditions. Patients with...The microbiome and host immune system maintain a dynamic homeostatic equilibrium at the skin interface. Prior studies have shown that the skin microbiome is profoundly altered in immunodeficient conditions. Patients with idiopathic CD4 lymphopenia, a rare clinical syndrome with an obscure cause, and people living with HIV are 2 etiologically distinct groups of individuals with CD4 T-cell lymphopenia. We conducted shotgun metagenomic sequencing, metagenome assembly, and read-based mapping to examine the multi-kingdom taxonomic diversity of skin microbiomes in patients with idiopathic CD4 lymphopenia and people living with HIV who were followed longitudinally before and after initiation of antiretroviral therapy. Compared with healthy individuals, the skin microbiomes of patients with idiopathic CD4 lymphopenia and antiretroviral therapy-naïve people living with HIV showed greater inter-individual variation and higher relative abundances of eukaryotic viruses. Both patient groups carried pathogenic microbes, including high-oncogenic-risk human papillomaviruses and dermatophytes such as Trichophyton rubrum, which were rarely seen in healthy controls. In people living with HIV, high-oncogenic-risk human papillomaviruses persisted after 2 months of antiretroviral therapy but were mostly cleared after 14 months. The loss of peripheral blood CD4 T-cells was associated with shifts in the skin microbiome and a relative expansion of pathogenic microbes. Investigating microbiome dynamics during immunodeficiency and subsequent immune reconstitution provides additional insights into host-microbial interactions.
UVR is a major public health concern, linked to skin cancer, eye damage, immune suppression, and premature aging. Yet, despite decades of innovation, the gold standard for sunscreen evaluation, sun protection factor and...UVR is a major public health concern, linked to skin cancer, eye damage, immune suppression, and premature aging. Yet, despite decades of innovation, the gold standard for sunscreen evaluation, sun protection factor and UVA protection factor testing in human volunteers, remains empirical, ethically questionable, and highly variable. In this study, we present an assay for UVA radiation assessment, a high-throughput, cell-based biosensor that luminesces in response to UVA exposure (320-400 nm). Assay for UVA radiation assessment-transgenic human cells express a membrane-anchored, photocleavable PhoCl domain fused to the tetracycline repressor and viral activator VP16, with nuclear export signals that ensure minimal basal activity. Upon UVA illumination, PhoCl cleavage liberates tetracycline repressor-VP16, which translocates to the nucleus and activates a tetracycline-responsive reporter. This molecular design enables sensitive detection of 365 nm and 395 nm light with up to 100-fold induction. By combining precision, reproducibility, and ethical advantages, assay for UVA radiation assessment establishes a powerful platform for the high-throughput testing of UV blockers and offers a transformative alternative to in vivo UVA protection factor assessment.
Vitiligo is an autoimmune disease characterized by depigmented skin lesions, caused by autoreactive-CD8-T-cells inducing melanocyte apoptosis. Effective treatment is challenging due to limited understanding of the proces...Vitiligo is an autoimmune disease characterized by depigmented skin lesions, caused by autoreactive-CD8-T-cells inducing melanocyte apoptosis. Effective treatment is challenging due to limited understanding of the processes underlying skin repigmentation. This study aimed to identify these processes using proteomics. Plasma and skin blister-fluid samples from 30 patients with vitiligo starting standard-of-care treatment were analyzed. A large proteomic screen of 5080 proteins was measured with Somascan on samples collected at baseline and at 3 months of treatment. Analyses of proteins that changed and did not change under treatment, revealed 5 proteins associated with repigmentation. Higher baseline levels of T-cell immunoglobulin and mucin domain 1, trefoil factor 3, and NACHT, LRR and PYD domains-containing protein 1 in blister-fluid and an increase of keratin type II cytoskeletal 5 in plasma under treatment, were associated with repigmentation. T-cell immunoglobulin and mucin domain 1 and trefoil factor 3 have immunosuppressive effects, while NACHT, LRR and PYD domains-containing protein 1 and keratin type II cytoskeletal 5 can stimulate melanogenesis. The NACHT, LRR and PYD domains-containing protein 1-inflammasome pathway was enriched in these proteins. These proteins and pathways were distinct from the previously identified differences between lesional and non-lesional skin, indicating differential expression of melanocyte-specific pathways. This suggests that treatment-induced repigmentation in vitiligo involves processes other than simply reversing lesional skin to a non-lesional state. These findings enhance the understanding of repigmentation in vitiligo and could guide future therapeutic strategies.