Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis.

Autor: Alkon N; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Assen FP; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Arnoldner T; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Bauer WM; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Medjimorec MA; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Shaw LE; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Rindler K; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Holzer G; Department of Dermatology, Klinik Donaustadt, Vienna, Austria., Weber P; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Weninger W; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Freystätter C; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria., Chennareddy S; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY., Kinaciyan T; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Farlik M; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Jonak C; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Griss J; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Bangert C; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Brunner PM; Department of Dermatology, Medical University of Vienna, Vienna, Austria; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: patrick.brunner@mountsinai.org.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Aug; Vol. 152 (2), pp. 420-435. Date of Electronic Publication: 2023 May 18.
DOI: 10.1016/j.jaci.2023.04.019
Abstrakt: Background: Chronic nodular prurigo (CNPG) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuroimmunological dysregulation. This condition may be associated with atopy in some patients, and there are now promising therapeutic results from blocking type 2 cytokines such as IL-4, IL-13, and IL-31.
Objectives: This study aimed to improve the understanding of pathomechanisms underlying CNPG as well as molecular relationships between CNPG and atopic dermatitis (AD).
Methods: We profiled skin lesions from patients with CNPG in comparison with AD and healthy control individuals using single-cell RNA sequencing combined with T-cell receptor sequencing.
Results: We found type 2 immune skewing in both CNPG and AD, as evidenced by CD4 + helper T cells expressing IL13. However, only AD harbored an additional, oligoclonally expanded CD8A + IL9R + IL13 + cytotoxic T-cell population, and immune activation pathways were highly upregulated in AD, but less so in CNPG. Conversely, CNPG showed signatures of extracellular matrix organization, collagen synthesis, and fibrosis, including a unique population of CXCL14 - IL24 + secretory papillary fibroblasts. Besides known itch mediators such as IL31 and oncostatin M, we also detected increased levels of neuromedin B in fibroblasts of CNPG lesions compared with AD and HC, with neuromedin B receptors detectable on some nerve endings.
Conclusions: These data show that CNPG does not harbor the strong disease-specific immune activation pathways that are typically found in AD but is rather characterized by upregulated stromal remodeling mechanisms that might have a direct impact on itch fibers.
(Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: