The following is a summary of “Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab,” published in the January 2024 issue of Allergy & Immunology by Ma, et al.
For a study, researchers sought to comprehensively investigate the molecular pathogenesis of prurigo nodularis (PN) at the single-cell level, distinguishing it from atopic dermatitis skin and evaluating the impact of the IL31RA antagonist, nemolizumab.
Skin samples from 15 healthy donors and nonlesional and lesional skin from 6 PN and 6 atopic dermatitis patients were subjected to single-cell RNA-sequencing. Spatial sequencing using the 10x Visium platform was also conducted. Additionally, bulk RNA-sequencing data from PN patients treated with nemolizumab were integrated.
The study revealed that PN is characterized by inflammation, keratinocyte proliferation, and activation of profibrotic responses. Notably, a subset of COL11A1+ fibroblasts, primarily located in the papillary dermis, was identified as a key contributor to fibrosis in PN skin. Furthermore, activation of fibrotic responses was found to be the primary distinguishing feature between PN and atopic dermatitis skin. Importantly, nemolizumab broadly affected PN cell types, particularly driving the normalization of COL11A1+ fibroblast and keratinocyte responses.
The study provided a comprehensive understanding of the cellular and molecular mechanisms underlying PN, highlighting its nature as a chronic fibrotic inflammatory skin disease. Moreover, it underscores the potential therapeutic efficacy of nemolizumab in targeting pathological processes in PN skin.
Reference: jacionline.org/article/S0091-6749(23)00925-9/fulltext