A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome.

Guard proteins initiate defense mechanisms upon sensing pathogen-encoded virulence factors. Successful viral pathogens likely inhibit guard protein activity, but these interactions have been largely undefined. Here, we demonstrate that the human pathogen herpes simplex virus 1 (HSV-1) stimulates and inhibits an antiviral pathway initiated by NLRP1, a guard protein that induces inflammasome formation and pyroptotic cell death when activated.

The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus.

The autoimmune disease lupus erythematosus (lupus) is characterized by photosensitivity, where even ambient ultraviolet radiation (UVR) exposure can lead to development of inflammatory skin lesions. We have previously shown that Langerhans cells (LCs) limit keratinocyte apoptosis and photosensitivity via a disintegrin and metalloprotease 17 (ADAM17)-mediated release of epidermal growth factor receptor (EGFR) ligands and that LC ADAM17 sheddase activity is reduced in lupus. Here, we sought to understand how the lupus skin environment contributes to LC ADAM17 dysfunction and, in the process, differentiate between effects on LC ADAM17 sheddase function, LC ADAM17 expression, and LC numbers.

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease.

Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics.

Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin.

Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved.

Evaluating the use of JAK inhibitors in inflammatory connective tissue diseases in pediatric patients: an update.

Introduction: Connective tissue diseases (CTDs) are a category of conditions that affect tissues that support and provide structure to the body. These diseases include rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, and sclerosing diseases. CTDs can be caused by dysregulation of inflammatory pathways, specifically an upregulation of interferons and JAK/STAT pathway activation.

The Impact of Telehealth Implementation on Underserved Populations and No-Show Rates by Medical Specialty During the COVID-19 Pandemic.

A unique and sudden need for virtual medical visits created by the coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented expansion of telemedicine across nearly all medical specialties in the United States. In addition to providing essential medical services during the pandemic, telemedicine has the potential to expand health care access to underserved populations by eliminating traditional barriers to care such as transportation needs, distance from specialty providers, and approved time off from work. However, the literature regarding telehealth accessibility for low-income, non-English-speaking, and minority patients remains limited.

Successful treatment of progressive macular hypomelanosis.

Progressive Macular Hypomelanosis (PMH) is a common but often misdiagnosed disorder of acquired hypopigmentation. An adolescent female presented with irregular, hypopigmented patches ultimately diagnosed as PMH. Complete repigmentation was achieved with narrowband UVB phototherapy, benzoyl peroxide wash, and clindamycin lotion.

Ovoid palatal patch: a clue to anti-TIF1γ dermatomyositis.

An 80-year-old woman presented with a several-year history of progressive hair loss and scalp pruritus. No other rashes or muscle weakness were noted on examination. Scalp biopsy showed interface dermatitis, dense perivascular and periadnexal lymphocytic infiltrate, mucin and scarring alopecia.

Resident Memory and Recirculating Memory T Cells Cooperate to Maintain Disease in a Mouse Model of Vitiligo.

Tissue resident memory T cells (Trm) form in the skin in vitiligo and persist to maintain disease, as white spots often recur rapidly after discontinuing therapy. We and others have recently described melanocyte-specific autoreactive Trm in vitiligo lesions. Here, we characterize the functional relationship between Trm and recirculating memory T cells (Tcm) in our vitiligo mouse model.

Vitiligo Pathogenesis and Emerging Treatments.

The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte destruction. The goal of treatment is to not only halt disease progression but also promote repigmentation through melanocyte regeneration, proliferation, and migration. Treatment strategies that address all aspects of disease pathogenesis and repigmentation are likely to have greatest efficacy, a strategy that may require combination therapies.

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

Background: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.

Objective: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.

Methods: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid.

Understanding autoimmunity of vitiligo and alopecia areata.

Purpose Of Review: Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments.