Ariana Moreno’s research while affiliated with Rockefeller University and other places

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow‐cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL‐17RA ⁺ eosinophils were highly and significantly correlated with multiple HS‐related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T‐ and B‐cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL‐17A/IL‐17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17‐related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease.

Introduction Atopic dermatitis (AD) is an inflammatory disease affecting over 20% of the pediatric population, with 85% of cases presenting before the age of five. Recently, therapeutic options in pediatric patients have evolved rapidly, following extensive development in adult treatments. Areas covered This review will encompass relevant molecular drivers, along with an overlook on treatment modalities in pediatric AD, as well as a summary of pipeline treatments in clinical trials for pediatric patients from PubMed, Google Scholar, and Clinicaltrials.gov up to July 2022. Topical corticosteroids are the mainstay for AD flares in adults and children. Topical approved agents in pediatric AD are calcineurin inhibitors, crisaborole and ruxolitinib. Dupilumab is the only FDA approved biologic for patients with AD from six months of age. A Janus kinase inhibitor, upadacitinib, is a systemic treatment approved for pediatric AD patients (age >12 years). Systemic immunosuppressants used in pediatric AD include methotrexate, azathioprine, cyclosporine and mycophenolate mofetil. Expert opinion Data regarding disease prevention are conflicting, however, an abundance of research has transpired regarding amelioration of symptoms and induction of disease clearance by targeting numerous pathological mechanisms. Understanding the pediatric AD phenotype will further advance the field and the development of improved therapeutics.

Psoriasis vulgaris is a common inflammatory disease affecting 7.5 million adults just in the US. Previously, psoriasis immunopathogenesis has been viewed as the imbalance between CD4⁺ T-helper 17 (Th17) cells and regulatory T-cells (Tregs). However, current paradigms are rapidly evolving as new technologies to study immune cell subsets in the skin have been advanced. For example, recently minted single-cell RNA sequencing technology has provided the opportunity to compare highly differing transcriptomes of Type 17 T-cell (T17 cell) subsets depending on IL-17A vs. IL-17F expression. The expression of regulatory cytokines in T17 cell subsets provided evidence of T-cell plasticity between T17 cells and regulatory T-cells (Tregs) in humans. In addition to Tregs, other types of regulatory cells in the skin have been elucidated, including type 1 regulatory T-cells (Tr1 cells) and regulatory dendritic cells. More recently, investigators are attempting to apply single-cell technologies to clinical trials of biologics to test if monoclonal blockade of pathogenic T-cells will induce expansion of regulatory immune cell subsets involved in skin homeostasis.