The following is a summary of “Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis,” published in the AUGUST 2023 issue of Allergy (& Immunology) by Alkon, et al.
Chronic nodular prurigo (CNPG) is an inflammatory skin condition that persists due to a chronic itch-scratch cycle, likely influenced by neuroimmunological dysregulation. The disorder may be associated with atopy in certain patients, and recent therapeutic advancements involve targeting type 2 cytokines such as IL-4, IL-13, and IL-31. For a study, researchers sought to enhance the understanding of the underlying pathomechanisms of CNPG and explore molecular connections between CNPG and atopic dermatitis (AD).
Skin lesions from CNPG patients were profiled and compared with AD and healthy control individuals using single-cell RNA sequencing coupled with T-cell receptor sequencing.
Both CNPG and AD exhibited type 2 immune skewing, as evidenced by the presence of CD4+ helper T cells expressing IL13. However, only AD displayed an additional oligoclonally expanded CD8A+IL9R+IL13+ cytotoxic T cells. Immune activation pathways were prominently upregulated in AD but less so in CNPG. In contrast, CNPG exhibited signatures related to extracellular matrix organization, collagen synthesis, and fibrosis. Notably, a distinctive subset of secretory papillary fibroblasts expressing CXCL14–IL24+ was found in CNPG. Alongside established itch mediators like IL31 and oncostatin M, increased levels of neuromedin B were detected in fibroblasts of CNPG lesions compared to AD and healthy controls. Neuromedin B receptors were also identified on some nerve endings.
The study highlighted that CNPG lacks the robust disease-specific immune activation pathways commonly observed in AD. Instead, CNPG is characterized by heightened stromal remodeling mechanisms, which could directly impact itch fibers.