Study unravels novel therapeutic option for the treatment of psoriasis

A group of clinical experts and international scientists have revealed a novel cell type in human skin that contributes to inflammatory skin diseases like psoriasis (PSO) and atopic dermatitis (AD). The research observations were published recently in the Journal of Experimental Medicine.

PsoriasisImage Credit: SNAB/Shutterstock.com

The researchers are from A*STAR’s Singapore Immunology Network (SIgN), in association with the Skin Research Institute of Singapore (SRIS), Singapore’s National Skin Centre, Department of Dermatology, Kyoto University Graduate School of Medicine, Japan, and industry partner Galderma.

Chronic inflammatory skin diseases like PSO and AD are marked by the presence of activated T cell subtypes producing pro-inflammatory cytokines in the skin. This T cell-mediated immune dysregulation is crucial to the pathogenesis of a broad range of inflammatory skin diseases.

Thus, a thorough knowledge of the factors modulating T cell priming and activation in healthy and diseased skin is vital to the advancement of efficient treatments for these diseases.

Currently, the single-cell RNA sequencing (RNA-seq) method is employed to examine immune cells in human skin, including dendritic cells (DCs) and macrophages—cell populations governing T cell activation.

To address the role of macrophages and DCs in chronic inflammatory skin diseases, the researchers employed a combination of complex methods (RNA-seq of index-sorted cells and single-cell flow cytometry from both diseased and healthy human skin) to develop an unbiased profile/landscape of macrophages and DCs, and to elaborate their definite molecular signatures and proportions in skin lesions of PSO and AD patients.

This unearthed a crucial enrichment in the proportion of CD14+ DC3s in PSO lesional skin, where they were one of the prominent cell types co-expressing IL1B and IL23A—two cytokines vital for PSO pathogenesis.

This observation put forth that targeting CD14+ DC3 might depict a new therapeutic choice in the treatment of PSO and illustrates the possibility for the single-cell myeloid cell landscape database to offer significant insights into skin biology in health and disease.

The findings from this study are significant as it will allow the design of new strategies to target or modulate myeloid cell populations for better health outcomes for patients of atopic dermatitis and psoriasis.”

Dr Florent Ginhoux, Study Last Author and Senior Principal Investigator, Singapore Immunology Network, Agency for Science, Technology and Research

Professor Kenji Kabashima Adjunct Principal Investigator from SIgN and SRIS states, “The roles of antigen-presenting cells in the development of inflammatory skin diseases remain unclear.”

This study clearly revealed the functions of each antigen-presenting cell subset, which is very informative and valuable to understand the pathogenesis of atopic dermatitis and psoriasis. We expect that this study will lead to the design of new treatment for refractory inflammatory skin diseases.”

Professor Kenji Kabashima, Adjunct Principal Investigator, Skin Research Institute of Singapore, Agency for Science, Technology and Research

Source:
Journal reference:

Nakamizo, S., et al. (2021) Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis. Journal of Experimental Medicine. doi.org/10.1084/jem.20202345.

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