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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Characterization of high and low IFNG-expressing subgroups in atopic dermatitis.
Int. J. Mol. Sci. 25:6158 (2024)
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Ifn-γ ; Ifng ; Il-4ra1 ; M1 Macrophages ; Atopic Dermatitis ; Natural Killer Cells ; Subgroups/endotypes; Recombinant Interferon-gamma; Skin; Therapy; Interleukin-4; Apoptosis; Cytokines; Subsets; Immune; Il-4
ISSN (print) / ISBN
1422-0067
e-ISSN
1661-6596
Quellenangaben
Volume: 25,
Issue: 11,
Article Number: 6158
Publisher
MDPI
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute for Allergy Research (IAF)
Grants
European Research Council
Technical University of Munich
Deutsche Forschungsgemeinschaft
European Research Council
Technical University of Munich
Deutsche Forschungsgemeinschaft