„Autoallergy“ in atopic dermatitis Susanne Hradetzky Lennart Roesner Division of Immunodermatology and Allergy Research Department of Dermatology and Allergy Autoallergy Autoallergens „classical“ autoantigens with IgE reactivity Collagen (rheumatoid arthritis) Thyreoperoxidase (Hashimoto‘s Thyreoditis) BP230 (Bullous Pemphigoid) Autoallergens without known cross-reactivity to exogenous allergens Hom s 1 (SART-1) Hom s 2 (α-NAC) Hom s 3 (BCL7B, Oncogen) Hom s 4 (Calcium-binding) Hom s 5 (Cytokeratin II) Introduction Autoallergens with cross-reactivity to exogenous allergens Profilin (Panallergen) MnSOD (A. fumigatus) Thioredoxin (M. sympodialis) Stimulation of sensitized patients´ PBMC with a-NAC induces specific proliferation of skin-homing T cells CD4+ als well as CD8+ a-NAC-specific T cell clones can be generated IL-10 secretion is reduced in PBMCs from sensitized AD patients IL-10 in PBMC, monocyte and CD4+ T cell supernatants n=5 1500 PBMCs monocytes CD4+ T cells 500 200 150 100 50 0 Med α-NAC α-NAC + IL-2 IL-10 in PBMC supernatants IL-2 IL-10 [pg/ml] IL-10 [pg/ml] 1000 3000 2500 2000 1500 1000 500 500 400 300 200 100 0 * ns ** M ed Results * NA C ** AD: n=11 ctrl: n=18 AD ns: n=12 * N A C + IL -2 IL -2 α-NAC activates monocytes via TLR-2 IL-12 p40 [pg/ml] IL-12 p40 in monocyte supernatants ** 400 350 300 250 200 150 150 * n=9 100 50 0 Preincubation Stimulation - Results anti- Isotype TLR2 α-NAC - anti- Isotype TLR2 α-NAC + IL-2 α-NAC and hTrx trigger innate and T cell cytokine responses α-NAC α-NAC IL-2 TLR-2 TCR NLRP3 IL-1β P-NFκB P-p44/42 P-STAT3 P-STAT3 IL-12 IL-23 IL-6 T cell IFN-γ IL-17 IL-22 IL-13 Conclusion IL-10 Monocyte Hannover Medical School (MHH) Div. of Immundermatology and Allergy Research Department of Dermatology and Allergy [email protected] [email protected] www.mh-hannover.de/Immundermatologie.html Prof. Dr. Rudolf Valenta Dr. Irene Mittermann Prof. Dr. Thomas Werfel Dr. Susanne Hradetzky Division of Immunopathology, Department of Pathophysiology and Allergy Research Centre for Pathophysiology, Infectiology and Immunology Medical University of Vienna, Austria Dr. Lennart Rösner Prof. Dr. Reto Crameri Dr. Annice Heratizadeh Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland Gabi Begemann Petra Kienlin Prof. Dr. Annika Scheynius Department of Medicine Solna, Clinical Allergy Research Unit, Karolinska Institutet, Stockholm, Sweden
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