Neurological diseases continue to increase in prevalence worldwide. Combined with the lack of modifiable risk factors or strongly efficacious therapies, these disorders pose a significant and growing burden on healthcare systems and societies. The development of neuroprotective or curative therapies is limited by a variety of factors, but none more than the highly selective blood-brain barrier. Intranasal administration can bypass this barrier completely and allow direct access to brain tissues, enabling a large number of potential new therapies ranging from bioactive peptides to stem cells. Current research indicates that merely administering simple solutions is inefficient and may limit therapeutic success. While many therapies can be delivered to some degree without carrier molecules or significant modification, a growing body of research has indicated several methods of improving the safety and efficacy of this administration route, such as nasal permeability enhancers, gelling agents, or nanocarrier formulations. This review shall discuss promising delivery systems and their role in expanding the clinical efficacy of this novel administration route. Optimization of intranasal administration will be crucial as novel therapies continue to be studied in clinical trials and approved to meet the growing demand for the treatment of patients with neurological diseases.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting cellular adhesion molecules. While IgE autoantibodies are occasionally reported in other autoimmune blistering diseases, BP is unique in that most BP patients develop an IgE autoantibody response. It is not known why BP patients develop self-reactive IgE and the precise role of IgE in BP pathogenesis is not fully understood. However, clinical evidence suggests an association between elevated IgE antibodies and eosinophilia in BP patients. Since eosinophils are multipotent effector cells, capable cytotoxicity and immune modulation, the putative interaction between IgE and eosinophils is a primary focus in current studies aimed at understanding the key components of disease pathogenesis. In this review, we provide an overview of BP pathogenesis, highlighting clinical and experimental evidence supporting central roles for IgE and eosinophils as independent mediators of disease and via their interaction. Additionally, therapeutics targeting IgE, the Th2 axis, or eosinophils are also discussed.

Ebola virus (EBOV) causes severe human disease. During late infection, EBOV virions are on the skin’s surface; however, the permissive skin cell types and the route of virus translocation to the epidermal surface are unknown. We describe a human skin explant model and demonstrate that EBOV infection of human skin via basal media increases in a time-dependent and dose-dependent manner. In the dermis, cells of myeloid, endothelial, and fibroblast origin were EBOV antigen–positive whereas keratinocytes harbored virus in the epidermis. Infectious virus was detected on the apical epidermal surface within 3 days, indicating that virus propagates and traffics through the explants. Purified human fibroblasts and keratinocytes supported EBOV infection ex vivo and both cell types required the phosphatidylserine receptor, AXL, and the endosomal protein, NPC1, for virus entry. This platform identified susceptible cell types and demonstrated dynamic trafficking of EBOV virions. These findings may explain person-to-person transmission via skin contact.

Bullous pemphigoid (BP) is an autoimmune blistering disease of the elderly who are frequently colonised by Staphylococcus aureus , particularly strains producing the superantigen toxic shock syndrome toxin‐1 (TSST‐1). Given the ability of TSST‐1 to engage the T cell receptor (TCR) Vβ2 chain, we investigated whether superantigen (SAg) exposure in BP is associated with alterations in peripheral T cell populations. CD4 ⁺ T cells were isolated from peripheral blood mononuclear cells (PBMCs) from BP patients and age‐matched healthy controls. T cell responsiveness to TSST‐1, staphylococcus enterotoxin G (SEG), and staphylococcus enterotoxin‐like‐I (SEl‐I) was assessed via proliferation assays, and the TCR Vβ repertoire was analysed by RT‐qPCR of bulk CD4 ⁺ T cells and flow cytometry of conventional CD4 ⁺ , CD8 ⁺ , and regulatory T cell (Treg, CD4 ⁺ FoxP3 ⁺ ) subsets. Contrary to expectations, proliferative responses to TSST‐1 were significantly lower in BP samples than in controls, while responses to SEG and SEl‐I were comparable. RT‐qPCR revealed no expansion of Vβ2 ⁺ in bulk CD4 ⁺ T cells, and surface phenotyping detected no enrichment of Vβ2 ⁺ cells within conventional CD4 ⁺ or CD8 ⁺ T populations. In contrast, Vβ2 ⁺ cells were selectively enriched within the Treg compartment. These findings indicate that peripheral T cell responses to TSST‐1 are attenuated in BP and are associated with subset‐specific skewing of the TCR repertoire. These findings are consistent with increased regulatory features in the peripheral immune compartment that may limit systemic SAg reactivity. Studies examining lesional skin immune populations are needed to determine whether local T cell responses differ from those observed in peripheral blood.