@article{f1d1e6b8993245a4a88f4cf8091fbbac,
title = "Specific T cells targeting Staphylococcus aureus fibronectin-binding protein 1 induce a type 2/type 1 inflammatory response in sensitized atopic dermatitis patients",
abstract = "BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin-binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed-type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1-specific T cells as possible trigger factors in AD.METHODS: Immunodominant T-cell epitopes were mapped by proliferation testing of patient-derived FBP1-specific T-cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA-matched, IgE-sensitized AD patients.RESULTS: Cytokine profiling of multimer-sorted cells revealed that predominantly the type 2 cytokines IL-13 and IL-4 were secreted by these cells. In contrast, IL-17, the marker cytokine for response to extracellular pathogens, was scarcely detectable.CONCLUSIONS: We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro-inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients.",
keywords = "Carrier Proteins/metabolism, Cytokines/metabolism, Dermatitis, Atopic, Fibronectins/metabolism, Humans, Immunoglobulin E, Skin, Staphylococcal Infections/metabolism, Staphylococcus aureus",
author = "Farag, {Ahmed K} and Roesner, {Lennart M} and Susanne Wieschowski and Annice Heratizadeh and Britta Eiz-Vesper and Kwok, {William W} and Rudolf Valenta and Thomas Werfel",
note = "Funding Information: We would like to acknowledge Gabriele Begemann and Petra Kienlin for excellent technical assistance and in addition the assistance of the Cell Sorting Core Facility of the Hannover Medical School supported in part by Braukmann‐Wittenberg‐Herz‐Stiftung and Deutsche Forschungsgemeinschaft. Rudolf Valenta was supported by grant F4605 from the Austrian Science Fund (FWF) and is a recipient of a Megagrant of the Government of the Russian Federation, grant No 14.W03.31.0024. Parts of the study were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2155 – Project ID 390874280. Biorender was used for designing the illustration in the graphical abstract. Funding Information: Braukmann-Wittenberg-Herz-Stiftung and Deutsche Forschungsgemeinschaft. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany?s Excellence Strategy ? EXC 2155 ? Project ID 390874280. Austrian Science Fund (FWF) F4605. Megagrant of the Government of the Russian Federation 14.W03.31.0024. The country of Lower Austria, Danuber ARC We would like to acknowledge Gabriele Begemann and Petra Kienlin for excellent technical assistance and in addition the assistance of the Cell Sorting Core Facility of the Hannover Medical School supported in part by Braukmann-Wittenberg-Herz-Stiftung and Deutsche Forschungsgemeinschaft. Rudolf Valenta was supported by grant F4605 from the Austrian Science Fund (FWF) and is a recipient of a Megagrant of the Government of the Russian Federation, grant No 14.W03.31.0024. Parts of the study were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy ? EXC 2155 ? Project ID 390874280. Biorender was used for designing the illustration in the graphical abstract. Funding Information: Braukmann‐Wittenberg‐Herz‐Stiftung and Deutsche Forschungsgemeinschaft. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany{\textquoteright}s Excellence Strategy – EXC 2155 – Project ID 390874280. Austrian Science Fund (FWF) F4605. Megagrant of the Government of the Russian Federation 14.W03.31.0024. The country of Lower Austria, Danuber ARC Publisher Copyright: {\textcopyright} 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",
year = "2022",
month = apr,
doi = "10.1111/all.15120",
language = "English",
volume = "77",
pages = "1245--1253",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",
}