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  1. Book ; Thesis: Allergenspezifische T-Zell-Antwort bei Ekzemkrankheiten

    Werfel, Thomas

    (Fortschritte der Allergologie und Immunologie)

    2000  

    Author's details von Thomas Werfel
    Series title Fortschritte der Allergologie und Immunologie
    Keywords Kontaktdermatitis ; Cytokine ; T-Lymphozyt ; Struktur-Aktivitäts-Beziehung ; Endogenes Ekzem
    Subject Struktur-Wirkungs-Beziehung ; Struktur-Wirkung-Beziehung ; Struktur-Aktivität-Beziehung ; Struktur-Funktions-Beziehung ; Thymus-Lymphozyt ; T-Zelle ; T-Lymphozyt ; Thymozyt ; Zytokine ; Essentielles Ekzem ; Essenzielles Ekzem ; Konstitutionelles Ekzem ; Ekzema atopicum ; Atopisches Ekzem ; Dermatitis atopica ; Atopische Dermatitis ; Neurodermitis ; Neurodermitis constitutionalis
    Language German
    Size X, 106 S. : Ill., graph. Darst.
    Publisher Dustri-Verl. Feistle
    Publishing place München-Deisenhofen
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Hannover, Univ., Habil.-Schr., 1996
    HBZ-ID HT012744139
    ISBN 3-87185-293-7 ; 978-3-87185-293-0
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: T-cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease.

    Roesner, Lennart M / Farag, Ahmed K / Pospich, Rebecca / Traidl, Stephan / Werfel, Thomas

    Allergy

    2022  Volume 77, Issue 9, Page(s) 2737–2747

    Abstract: ... skin diseases in developed countries. A hallmark of both diseases is T-cell infiltration into the skin ... However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing ... T cells or unspecific heterogeneous bystander cells.: Methods: To elucidate this, T cells from lesional ...

    Abstract Background: Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T-cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells.
    Methods: To elucidate this, T cells from lesional skin and from blood of 9 AD and 10 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA
    Results: Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T-cell clones were also detectable to a larger extent among CLA
    Conclusions: Our data show that in line with the systemic nature of psoriasis, T-cell clones that infiltrate psoriatic skin lesions do not exclusively possess skin-homing ability and are therefore most probably specific to antigens that are not exclusively expressed or located in the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.
    MeSH term(s) Allergens ; Antigens, Differentiation, T-Lymphocyte ; Antigens, Neoplasm ; Dermatitis, Atopic ; Humans ; Leukocytes, Mononuclear/metabolism ; Membrane Glycoproteins ; Psoriasis ; Receptors, Antigen, T-Cell/genetics ; Receptors, Lymphocyte Homing
    Chemical Substances Allergens ; Antigens, Differentiation, T-Lymphocyte ; Antigens, Neoplasm ; Membrane Glycoproteins ; Receptors, Antigen, T-Cell ; Receptors, Lymphocyte Homing
    Language English
    Publishing date 2022-03-14
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Histamine H2 receptor stimulation upregulates T

    Mommert, Susanne / Gregor, Karl / Rossbach, Kristine / Schaper, Katrin / Witte, Torsten / Gutzmer, Ralf / Werfel, Thomas

    The Journal of allergy and clinical immunology

    2017  Volume 141, Issue 2, Page(s) 782–785.e5

    MeSH term(s) Chemokine CCL17/immunology ; Histamine Agonists/pharmacology ; Humans ; Macrophages/cytology ; Macrophages/immunology ; Receptors, Histamine H2/immunology ; Th2 Cells/immunology ; Up-Regulation/drug effects ; Up-Regulation/immunology
    Chemical Substances CCL17 protein, human ; Chemokine CCL17 ; Histamine Agonists ; Receptors, Histamine H2
    Language English
    Publishing date 2017-07-18
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2017.06.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Online ; Thesis: Investigating the role of embryonic γδ T cells and their T cell receptors at barrier sites

    Binz, Christoph [Verfasser] / Prinz, Immo [Akademischer Betreuer] / Werfel, Thomas [Akademischer Betreuer] / Sandrock, Inga [Akademischer Betreuer]

    2022  

    Author's details Christoph Binz ; Akademische Betreuer: Immo Prinz, Thomas Werfel, Inga Sandrock ; Hannover Biomedical Research School, Institut für Immunologie
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Bibliothek der Medizinischen Hochschule Hannover
    Publishing place Hannover
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  5. Article: Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein.

    Roesner, L M / Swiontek, K / Lentz, D / Begemann, G / Kienlin, P / Hentges, F / Ollert, M / Werfel, T / Hilger, C

    Journal of investigational allergology & clinical immunology

    2021  Volume 32, Issue 5, Page(s) 383–392

    Abstract: ... crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized ... differ from non-cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T ...

    Abstract Background: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander.
    Methods: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD.
    Results: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non-cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin.
    Conclusions: The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins.
    MeSH term(s) Allergens ; Animals ; Cats ; Cystatin A ; DNA, Complementary ; Dander ; Dermatitis, Atopic ; Dogs ; Humans ; Immunoglobulin E ; Interleukin-4 ; Mammals/genetics ; T-Lymphocytes
    Chemical Substances Allergens ; Cystatin A ; DNA, Complementary ; Interleukin-4 (207137-56-2) ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2021-09-07
    Publishing country Spain
    Document type Journal Article
    ZDB-ID 1128657-x
    ISSN 1018-9068
    ISSN 1018-9068
    DOI 10.18176/jiaci.0737
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: RNase 7 downregulates TH2 cytokine production by activated human T cells.

    Kopfnagel, V / Wagenknecht, S / Brand, L / Zeitvogel, J / Harder, J / Hofmann, K / Kleine, M / Werfel, T

    Allergy

    2017  Volume 72, Issue 11, Page(s) 1694–1703

    Abstract: ... such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and ... effects of the antimicrobial peptide RNase 7 on activated T cells.: Methods: Isolated human CD3+T cells ... that GATA3 activation was diminished upon cultivation of T cells with RNase 7.: Conclusion: Our data ...

    Abstract Background: The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMPs. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T cells.
    Methods: Isolated human CD3+T cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T cells and in polarized TH2 cells using skin-derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.
    Results: Treatment of activated human CD4+T cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T cells with RNase 7.
    Conclusion: Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.
    Language English
    Publishing date 2017-11
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.13173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Specific T cells targeting Staphylococcus aureus fibronectin-binding protein 1 induce a type 2/type 1 inflammatory response in sensitized atopic dermatitis patients.

    Farag, Ahmed K / Roesner, Lennart M / Wieschowski, Susanne / Heratizadeh, Annice / Eiz-Vesper, Britta / Kwok, William W / Valenta, Rudolf / Werfel, Thomas

    Allergy

    2021  Volume 77, Issue 4, Page(s) 1245–1253

    Abstract: ... 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 ... stained T helper cells in 8 out of 8 HLA-matched, IgE-sensitized AD patients.: Results: Cytokine ...

    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.
    MeSH term(s) Carrier Proteins/metabolism ; Cytokines/metabolism ; Dermatitis, Atopic ; Fibronectins/metabolism ; Humans ; Immunoglobulin E ; Skin ; Staphylococcal Infections/metabolism ; Staphylococcus aureus
    Chemical Substances Carrier Proteins ; Cytokines ; Fibronectins ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2021-10-22
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Foxp3(+) regulatory T cells are expanded in severe atopic dermatitis patients.

    Roesner, L M / Floess, S / Witte, T / Olek, S / Huehn, J / Werfel, T

    Allergy

    2015  Volume 70, Issue 12, Page(s) 1656–1660

    Abstract: Regulatory T cells (Tregs) are known to play critical roles in homeostasis and immune responses ... positive results as activated T cells without regulatory function may transiently upregulate ...

    Abstract Regulatory T cells (Tregs) are known to play critical roles in homeostasis and immune responses in the skin. Whether Treg frequencies are altered in atopic dermatitis (AD) patients has been addressed by several studies, leading to conflicting results. The detection of Tregs by FOXP3 expression may lead to false-positive results as activated T cells without regulatory function may transiently upregulate this transcription factor. In contrast, measurement of the DNA methylation status of a region within the FOXP3 locus that is selectively demethylated only in bona fide Tregs (Treg-specific demethylated region, TSDR) represents a reliable method to quantify Tregs. Here, we measured circulating Treg frequencies of adult patients and detected a positive correlation with disease severity. Subsequent surface marker analysis revealed higher frequencies of CD45RA(+) CCR7(-) tissue-homing Tregs in the patient group with a tendency of reduced expression of CD39 compared with healthy donors, a marker for the highly suppressive TREM subtype.
    MeSH term(s) Adult ; Dermatitis, Atopic/immunology ; Female ; Flow Cytometry ; Forkhead Transcription Factors/immunology ; Humans ; Immunophenotyping ; Male ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances FOXP3 protein, human ; Forkhead Transcription Factors
    Language English
    Publishing date 2015-12
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.12712
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book: Dupilumab bei atopischer Dermatitis

    Werfel, Thomas

    erstes Biologikum bei Erwachsenen mit schwerer atopischer Dermatitis

    (Drug report ; 12. Jahrgang, Heft 5 (Mai 2018))

    2018  

    Author's details Autor Prof. Dr. med. Thomas Werfel
    Series title Drug report ; 12. Jahrgang, Heft 5 (Mai 2018)
    Collection
    Language German
    Size 11 Seiten, Illustrationen, Diagramme
    Publisher Thieme
    Publishing place Stuttgart
    Publishing country Germany
    Document type Book
    HBZ-ID HT019710254
    Database Catalogue ZB MED Medicine, Health

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  10. Article ; Online: Efficacy of T-cell transcription factor-specific DNAzymes in murine skin inflammation models.

    Purath, Ulrich / Ibrahim, Rouba / Zeitvogel, Jana / Renz, Harald / Runkel, Frank / Schmidts, Thomas / Dobler, Dorota / Werfel, Thomas / Müller, Anke / Garn, Holger

    The Journal of allergy and clinical immunology

    2016  Volume 137, Issue 2, Page(s) 644–647.e8

    MeSH term(s) Animals ; DNA, Catalytic/genetics ; DNA, Catalytic/metabolism ; Dermatitis/genetics ; Dermatitis/immunology ; Dermatitis/metabolism ; Dermatitis/pathology ; Disease Models, Animal ; Mice ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances DNA, Catalytic ; Transcription Factors
    Language English
    Publishing date 2016-02
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2015.09.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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