Biology subjects

Payne, A. S.

Publications and source records attributed to Payne, A. S..

3 recordsLinked to original sources

bioRxiv2024

Pemphigus vulgaris autoantibodies induce an ER stress response

Desmosomes are intercellular junctions that mediate cell-cell adhesion and are essential for maintaining tissue integrity. Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease caused by autoantibodies (IgG) targeting desmoglein 3 (Dsg3), a desmosomal cadherin. PV autoantibodies cause desmosome disassembly and loss of cell-cell adhesion, but the molecular signaling pathways that regulate these processes are not fully understood. Using high- resolution time-lapse imaging of live keratinocytes, we found that ER tubules make frequent and persistent contacts with internalizing Dsg3 puncta in keratinocytes treated with PV patient IgG. Biochemical experiments demonstrated that PV IgG activated ER stress signaling pathways, including both IRE1 and PERK pathways, in cultured keratinocytes. Further, ER stress transcripts were upregulated in PV patient skin. Pharmacological inhibition of ER stress protected against PV IgG-induced desmosome disruption and loss of keratinocyte cell-cell adhesion, suggesting that ER stress may be an important pathomechanism and therapeutically targetable pathway for PV treatment. These data support a model in which desmosome adhesion is integrated with ER function to serve as a cell adhesion stress sensor that is activated in blistering skin disease.

cell biology↗

bioRxiv2021

Bacterial DNA on the skin surface overrepresents the viable skin microbiome

The skin microbiome provides vital contributions to human health. However, the spatial organization and viability of its bacterial components remain unclear. Here we apply culturing, imaging, and molecular approaches to human and mouse skin samples, and find that the skin surface is colonized by fewer viable bacteria than predicted by bacterial DNA levels. Instead, viable skin-associated bacteria are predominantly located in hair follicles and other cutaneous invaginations. Furthermore, we show that the skin microbiome has a uniquely low fraction of viable bacteria as compared to other human microbiome sites, indicating that most bacterial DNA on the skin surface is not associated with viable cells Additionally, a small number of bacterial families dominate each skin site and traditional sequencing methods overestimate both the richness and diversity of the skin microbiome. Finally, we performed an in-vivo skin microbiome perturbation-recovery study using human volunteers. Bacterial 16S rRNA gene sequencing revealed that, while the skin microbiome is remarkably stable even in the wake of aggressive perturbation, repopulation of the skin surface is driven by the underlying viable population. Our findings help explain the dynamics of skin microbiome perturbation, as bacterial DNA on the skin surface can be transiently perturbed but is replenished by a stable underlying viable population. These results address multiple outstanding questions in skin microbiome biology with significant implications for future efforts to study and manipulate it. Significance statementThis study provides a crucial update to the skin microbiome paradigm by showing that viable bacteria of the skin microbiome are primarily localized to hair follicles and other sub-cutaneous structures rather than the skin surface. The native distribution of skin-associated bacteria has not been previously evaluated, and here we show that the skin surface has few intact bacteria while deeper structures are replete with bacterial contents. We used orthogonal approaches to evaluate the source of bacterial DNA and the dynamics of bacterial repopulation on the skin surface to develop an updated model of the skin microbiome. By adjusting the current understanding of the skin microbiome to match this model, we will be able to address outstanding questions in the field.

microbiology↗

bioRxiv2018

Anti-BP180 Autoantibodies Are Present in Stroke and Recognize Human Cutaneous BP180 and BP180-NC16A

BackgroundCurrent evidence has revealed a significant association between bullous pemphigoid (BP) and neurological diseases (ND), including stroke, but the incidence of BP autoantibodies in patients with stroke has not previously been investigated.\n\nObjectiveOur study aims to assess BP antigen-specific antibodies in stroke patients.\n\nMethods100 patients with stroke and 100 healthy controls were randomly selected to measure anti-BP180/230 IgG autoantibodies by enzyme-linked immunosorbent assay (ELISA), salt split indirect immunofluorescence (IIF) and immunoblotting against human cutaneous BP180 and BP180-NC16A.\n\nResultsAnti-BP180 autoantibodies were found in 14(14.0%) patients with stroke and 5(5.0 %) of controls by ELISA (p<0.05). Sera from 13(13.0%) patients with stroke and 3(3.0 %) controls reacted with 180-kDa proteins from human cutis extract (p<0.05). 11(11.0%) of stroke and 2(2.0 %) of control sera recognized the human recombinant full length BP180 and NC16A (p<0.05). The anti-BP180-positive patients were significantly younger than the negative patients in stroke (p<0.001).\n\nLimitationsLongitudinal changes in antibody titers and long-term clinical outcome for a long duration were not fully investigated.\n\nConclusionDevelopment of anti-BP180 autoantibodies occur at a higher frequency after stroke, suggesting BP180 as a shared autoantigen in stroke with BP and providing novel insights into BP pathogenesis in aging.

neuroscience↗