Atopic dermatitis and skin diseaseToll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10
Section snippets
Mice
BALB/c, C57BL/6, DO11.10, OT-II, and signal transducer and activator of transcription 6 (Stat6)–deficient mice were purchased from Charles River (Sulzfeld, Germany) or the Jackson Laboratory (Bar Harbor, Me). Tlr2−/− BL/6 mice were provided by C. Kirschning (Duisburg, Germany) and backcrossed to the BALB/c background, MHCII−/− mice were provided by L. Klein (Munich, Germany), and Il4ra−/− mice were provided by A. Gessner (Erlangen, Germany). All mice were kept and bred under specific
Self-limited allergen-induced dermatitis is mediated by IL-4
Early immune reactions in AD skin are dominated by TH2 cells and cytokines and are believed to predispose the AD skin for colonization by bacteria, such as S aureus. As a model for the early phase of AD inflammation, OVA-specific IL-4–producing TH2 cells were intracutaneously transferred with or without OVA into the ears of naive mice. Ear swelling was determined as the change in skin thickness to quantify dermatitis. Transfer of TH2 cells with OVA provoked strong but self-limiting cutaneous
Discussion
AD is based on a complex genetic trait, with skin barrier defects being among the most frequent functional abnormalities.3, 28 The majority of patients with AD have increased IgE levels toward environmental antigens and TH2-biased T-cell immunity, which is based on both cutaneous barrier defects and an inherent immune bias toward TH2 immunity.2 A prerequisite for the development of AD inflammation is the initial recruitment of IL-4–producing TH2 cells to the skin on acute triggering factors,
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Matrix Metalloproteinase 9 Plays a Crucial Role in Inflammation and Itch in Allergic Contact Dermatitis by Regulating Toll-Like Receptor 2/1 Signaling
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2021, Brain, Behavior, and ImmunityCitation Excerpt :Disturbances of innate and adaptive immune responses were implicated in pathogenesis of AD (Boguniewicz and Leung, 2011; Weidinger et al., 2018). Innate TLR2 signaling not only promotes itch and pain but convert transient TH2 cell-mediated dermatitis into persistent inflammation which is linked to chronic human AD (Kaesler et al., 2014; Liu et al., 2012; Niebuhr et al., 2009; Wang et al., 2020). Thus, our findings herein provide an important insight into IL-13-promoted neuro-immune itch circuits, and may help to understand the function of IL-13Rα2 upregulated during certain types of infections associated with AD.
Advancements in Allergen Immunotherapy for the Treatment of Atopic Dermatitis
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Supported by contract research “Allergologie 2” of the Baden-Württemberg Stiftung (P-LS-AL2/4) and by grants of the Deutsche Forschungsgemeinschaft (DFG; BI696/10-1, B1696/5-1, BI696/5-2, SFB 685 A06, C01) and the Wilhelm Sander-Stiftung (2012.056.1).
Disclosure of potential conflict of interest: S. Kaesler has received research support from Deutsche Forschungsgemeinschaft and Landesstiftung Baden-Württemberg. Y. Skabytska has received research support from Deutsche Forschungsgemeinschaft (DFG; BI 696/10-1). M. Köberle has received research support from Deutsche Forschungsgemeinschaft (DFG BI 696/5-1 and DFG BI 696/5-2). K.-M. Chen has received research support from Baden-Württemberg Stiftung. E. Guenova is employed by Harvard Medical School/Brigham and Women's Hospital and has received research support from the German Research Foundation (GU1271/2-1). M. Röcken has received research support from Abbott Laboratories, Abbott Pharmaceuticals, Almirall Hermal, Bayer, Biogen, Bundesministerium für Bildung und Forschung, Celgene, Deutsche Dermatologische Gesellschaft, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, the European Union, Galderma, GlaxoSmithKline, Hokusai, Janssen Cilag, Johnson & Johnson, Lilly, MSD Sharp & Dohme, Novartis, Pfizer, Roche, Wilhelm Sander-Stiftung, AstraZeneca, Bristol-Myers Squibb, Philogen, and AB Science and has received personal fees from Almirall Hermal, Bayer Healthcare, Biogen Idec, MSD Sharp & Dohme, Regeneron, and Roche. T. Biedermann has received research support from Baden-Württemberg Stiftung and Deutsche Forschungsgemeinschaft; has received consultancy fees from Meda and Novartis; and has received personal fees from Janssen Cilag, ALK-Abelló, Biogen, Meda, Novartis, and Phadia/Thermo Fisher. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.