Local treatment with BPPcysMPEG reduces allergic airway inflammation in sensitized mice |
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| Authors: | S Knothe V Mutschler S Rochlitzer C Winkler T Ebensen CA Guzman J Hohlfeld A Braun M Muller |
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| Institution: | 1. Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department of Immunology, Allergology and Immunotoxicology, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany;2. Fraunhofer Institute for Toxicology and Experimental Medicine, Department of Clinical Airway Research, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany;3. Helmholtz Centre for Infection Research, Department of Vaccinology and Applied Microbiology, Inhoffenstr. 7, 38124 Braunschweig, Germany;1. BioTherapeutics Research Laboratory, University of Western Ontario, London, Ontario, Canada;2. Imaging Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada;3. Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada;4. Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada;5. Department of Medial Biophysics, University of Western Ontario, London, Ontario, Canada;6. Department of Surgery, University of British Columbia and Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada;7. Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;1. National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK;2. Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK;1. Radiation Dosimetry Team, Korea Atomic Energy Research Institute, P.O.Box 105, Yuseong, Daejeon, Republic of Korea;2. Department of Nuclear Engineering, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea;3. The Research Institute of Natural Science and Department of Physics, Gyeongsang National University, Jinju, Republic of Korea;2. Department of Radiology, Medical Physics, University Hospital Freiburg, Freiburg, Germany;3. INRIA, Asclepios Research Project, Cardiac Modelling, Sophia Antipolis, France;4. Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island;1. Dept. Internal Medicine, University Medical Center, Regensburg 93042, Germany;2. Dept. Pharmacology and Toxicology, University of Regensburg, Regensburg 93040, Germany;3. Dept. Visceral Surgery and Medicine, Gastroenterology, University Medical Center, Bern 3010, Switzerland;1. Deutsches Herzzentrum, Technische Universität, Lazarettstrasse 36, 80636 Munich, Germany;2. 1. Medizinische Klinik rechts der Isar, Technische Universität, Munich, Germany;3. Krankenhaus Barmherzige Brüder, Munich, Germany |
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| Abstract: | According to the hygiene hypothesis, triggering the immune system with microbial components during childhood balances the inherent Th2 bias. In contrast, specific immunotherapy involves exposure of the patient to the allergen in order to achieve desensitization to subsequent contact.In a human in vitro allergy model the potential of the TLR2/6 agonist BPPcysMPEG to modulate antigen presenting cells and allergen-specific immune responses was evaluated. Specific immunomodulation via co-administration of the allergen and BPPcysMPEG enhanced expression of co-stimulatory molecules on DC and increased secretion of the proinflammatory cytokine TNF-α. Acting as an adjuvant, BPPcysMPEG elevated allergen-specific immune responses in co-culture with autologous lymphocytes. Although administration of BPPcysMPEG alone enhanced expression of co-stimulatory molecules on DC, proliferation of autologous lymphocytes was not induced.Based on this finding, the potential of BPPcysMPEG to reduce allergic airway inflammation by preventive modulation of the innate immune system via TLR2/6 agonization was investigated in mice. Local administration of BPPcysMPEG altered cellular influx and cell composition in BAL fluid. Furthermore, the Th2-associated cytokines IL-4 and IL-5 were diminished. Allergen-specific restimulation of cells from mediastinal lymph nodes and splenocytes suggested an alteration of immune responses. The treatment with BPPcysMPEG induced a Th1-dominated cytokine milieu in mediastinal lymph nodes, while allergen-specific immune responses in splenocytes were diminished. The co-administration of allergen and BPPcysMPEG reduced cytokine secretion upon restimulation in mediastinal lymph nodes and splenocytes.From these data we conclude that BPPcysMPEG was able to influence the immune system with regard to subsequent allergen contact by TLR2/6 agonization. |
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