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AG Immunology of the Lung

Group Leader: PD Dr. Marcus Peters     

Inflammatory respiratory diseases can have various causes. Common ones are, e.g. allergic asthma, which in most cases is triggered by the inhalation of allergens, and chronic bronchitis (COPD), which is mostly caused by long-term tobacco consumption. Often these diseases worsen due to viral infections. Respiratory syncytial virus (RSV) and influenza viruses play an important role. During the chronification of the disease, remodelling of the airways occurs which can lead to irreversible fatal disease. In a project funded by the FoRUM programme of the Faculty of Medicine, we are investigating the role of the proinflammatory cytokine IL-17A secreted by T cells in airway remodelling of asthma. In project funded by the Mercator Research Center Ruhr "RIMUR" we are investigating the role of the cytokine WNT5A in the immune response and remodelling of asthma. Furthermore, we are investigating the role of this interesting cytokine, which is known to play a role in many developmental biological processes, in respiratory tract infections by RSV and in drug induced fibrosis of the lung (Figure 1).

For these studies, we use mouse models for inflammatory airway diseases, in particular asthma, bleomycin-induced fibrosis and RSV infection. Models for an inducible, targeted knock out of WNT5A in specific cell populations are used (Cre/lox system). To analyse airway inflammation, we use invasive (Flexivent) and non-invasive (whole body plethysmography) methods for lung function measurement, histological methods, quantitative PCR and flow cytometry.

In addition to the mechanisms of airway inflammation, we are interested in substances with immunomodulatory effects that can prevent the development of inflammation. In this research area, we are investigating oligosaccharides derived from arabinogalactan, a complex polysaccharide with immunomodulatory activity. We succeeded in synthetically producing immunomodulatory partial structures from arabinogalactan and showing that these molecules prevent the development of allergic asthma in murine models. The production and use of these molecules is protected by a patent of the Ruhr-Universität Bochum (WO2017093276A1) (Figure 2).

PubMed listed Publications (last ten years)

Weidinger D, Jacobsen J, Alish D, Uebner H, Heinen N, Greune L, Westhoven S, Jamal Jameel K, Krosbein J, Pfaender S, Taube C, Reuter S, Peters M, Hatt H, Knobloch J. Olfactory receptors impact pathophysiological process of lung diseases in bronchial epithelial cells. J. Eur J Cell Biol. 2024 Mar 30;103(2):151408. doi: 10.1016/j.eicb.2024.151408.

Reinehr S, Wulf J, Theile J, Schulte KK, Peters M, Fuchshofer R, Dick HB, Joachim SC. In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced. Front Immunol. 2024 Mar 7;15:1296178

Zhang H, Quintana J, Ütkür K, Adrian L, Hawer H, Mayer K, Gong X, Castanedo L, Schulten A, Janina N, Peters M, Wirtz M, Brinkmann U, Schaffrath R, Krämer U. Translational fidelity and growth of Arabidopsis require stress-sensitive diphthamide biosynthesis. Nat Commun. 2022 Jul 11;13(1):4009. doi: 10.1038/s41467-022-31712-7.

Schiffer M, Peters K, Peters M. Comparison of airway remodeling in two different endotypes of allergic asthma. Int Arch Allergy Immunol. 2022;183(7):714-725.

Bachmann L, Gallego Villarejo L, Heinen N, Marks D, Peters M, Müller T. Gene-edited fluorescent cerebral organoids to study human brain function and disease. CRISPR J. 2022 Feb 22;5(1):53-65.

Stiehm M and Peters M. Specific immunotherapy in a murine model of grass pollen (Phl p5) allergy. Front Allergy. 2021 Dec 16;2:777545.

Carmo-Fernandes A, Puschkarow M, Peters K, Gnipp S, Peters M. The Pathogenic Role of Smooth Muscle Cell-Derived Wnt5a in a Murine Model of Lung Fibrosis. Pharmaceuticals. 2021; 14(8):755. https://doi.org/10.3390/ph14080755.

Peters K and Peters M. The role of lectin receptors and their ligands in controlling allergic inflammation. Front Immunol. 2021; 12: 635411.

Funke L, Gnipp S, Ahrens M, Eisenacher M, Peters M, Sitek B, Bracht T. Quantitative analysis of proteome dynamics in a mouse model of asthma. 2021 Feb 7. doi: 10.1111/cea.13843. Online ahead of print.

Bannewitz C, Lenz-Habijan T, Lentz J, Peters M, Trösken V, Siebert S, Weber S, Theisen W, Henkes H, Monstadt H. Evaluation of Antithrombogenic pHPC on CoCr Substrates for Biomedical Applications. Coatings 2021, 11(1), 93.

Krumb M, Jäger M, Voss A, Immig L, Peters K, Kowalczyk D, Bufe A, Opatz T, Holst O, Vogel C and Peters M. Total Synthesis of a Partial Structure from Arabinogalactan and its Application for Allergy‐Prevention. Chem. Eur. J. 2021, 27:928 –933.

Mundorf A, Rommel S, Verheyen M, Mergia E, Peters M, Freund N. Cigarette smoke exposure has region-specific effects on GDAP1 expression in mouse hippocampus. Psychiatry Res. 2020 May 7;289:112979.

Peters M, Peters K, Bufe A. Regulation of lung immunity by dendritic cells: Implications for asthma, chronic obstructive pulmonary disease and infectious disease. Innate Immun. 2019; 25(6):326-36.

Henkes H, Bhogal P, Aguilar Pérez M, Lenz-Habijan T, Bannewitz C, Peters M, Sengstock C, Ganslandt O, Lylyk P, Monstadt H. Anti-thrombogenic coatings for devices in neurointerventional surgery: Case report and review of the literature. Interv Neuroradiol. 2019 Dec;25(6):619-627.

Peters M. A patent on the synthesis of arabino‐oligosaccharides for regulation of immune responses in the lung. Allergy. 2019 Dec;74(12):2547-2549.

Knobloch J, Panek S, Yanik S, Jameel KJ, Bendella Z, Jungck D, Bürger P, Bülthoff E, Struck B, Giannakis N, Rupp J, Kronsbein J, Peters M, Koch A. The monocyte-dependent immune response to bacteria is suppressed in smoking-induced COPD. J Mol Med (Berl). 2019 Jun;97(6):817-828.

Fettel J, Kühn B, Guillen NA, Sürün D, Peters M, Bauer R, Angioni C, Geisslinger G, Schnütgen F, Meyer Zu Heringdorf D, Werz O, Meybohm P, Zacharowski K, Steinhilber D, Roos J, Maier TJ. Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity. FASEB J. 2019 Feb;33(2):1711-1726.

Gnipp S, Mergia E, Puschkarow M, Bufe A, Koesling D and Peters M.  Nitric oxide dependent signaling via cyclic GMP in dendritic cells regulates migration and T-cell polarization. Sci Rep. 2018 Jul 20;8(1):10969.

Lenz-Habijan T, Bhogal P, Peters M, Bufe A, Martinez Moreno R, Bannewitz C, Monstadt H, Henkes H. Hydrophilic stent coating inhibits platelet adhesion on stent surfaces: initial results in vitro. Cardiovasc Intervent Radiol. 2018 Nov;41(11):1779-1785.

Roos J*, Peters M*, Maucher IV, Kühn B, Fettel J, Hellmuth N, Brat C, Sommer B, Urbschat A, Piesche M, Vogel A, Proschak E, Blöcher R, Buscato E, Häfner AK, Matrone C, Werz O, Heidler J, Wittig I, Angioni C, Geisslinger G, Parnham MJ, Zacharowski K, Steinhilber D, Maier TJ. Drug-mediated intracellular donation of nitric oxide potently inhibits 5-lipoxygenase: a possible key to future anti-leukotriene therapy. Antioxid Redox Signal. 2018 May 10;28(14):1265-1285. *equal contribution

Peters M, Bonowitz P, Bufe A. A Bioassay for the Determination of Lipopolysaccharides and Lipoproteins. Methods Mol Biol. 2017;1600:143-150.

Maaske A, Devos FC, Niezold A, Lapuente D, Tannapfel A, Vanoirbeek JA, Überla K, Peters M, Tenbusch M. Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice. J Control Release. 2016; 237:14-22.

Kuehn S, Stellbogen M; Noristani R, Peters M, Dick HB, Joachim SC. Systemic ocular antigen immunization leads only to a minor secondary immune response. J Neuroimmunol. 2016; 293:114-22.

Peters M, Köhler-Bachmann S, Lenz-Habijan T, Bufe A. Influence of an allergen-specific Th17 response on remodeling of the airways. Am J Respir Cell Mol Biol. 2016; 54(3):350-358.

Peters M, Guidato PM, Peters K, Megger DA, Sitek B, Classen B, Heise EM, Bufe A. Allergy-protective arabinogalactan modulates human dendritic cells via c-type-lectins and inhibition of NFkB. J Immunol. 2016; 196(4):1626-35.

Stiehm M, Peters K, Wiesmüller KH, Bufe A, Peters M. A novel synthetic lipopeptide is allergy-protective by the induction of LPS-tolerance. Clin Exp All 2013; 43(7):785-97.

Stiehm M, Bufe A, Peters M. Proteolytic activity in cowshed dust extracts induces C5a release in murine bronchoalveolar lavage fluids which may account for its protective properties in allergic airway inflammation. Thorax 2013; 68(1):31-8.

Peters M, Dudziak K, Stiehm M, Bufe A. T-cell polarization depends on concentration of the danger signal used to activate dendritic cells. Immunol Cell Biol 2010; 88(5):537-44.

Vautz W, Nolte J, Bufe A, Baumbach JI, Peters M. Analyses of Mice’s Breath using Ion Mobility Spectrometry - A Feasibility Study. J Appl Physiol. 2010; 108(3); 697-704.

Peters M, Kauth M, Scherner O, Gehlhar K, Steffen I, Wentker P, von Mutius E, Holst O, Bufe A.

Arabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization. J. Allergy Clin. Immunol. 2010; 126(3):648-56.e1-4

Peters M, Bufe A. Arabinogalaktane aus Gräsern schützen vor der Entstehung von allergischen Erkrankungen. Allergologie 2011; 34(9):461-466.

Neuhaus S, Seifert L, Vautz W, Nolte J, Bufe A, Peters M. Comparison of metabolites in exhaled breath and bronchoalveolar lavage fluid samples in a mouse model of asthma. J Appl Physiol. 2011 Oct;111(4):1088-95.

Peters M, Bufe A. Vom Stallstaub zum Molekül: Mechanismen der allergieprotektiven Wirkung. Allergo J. 2011; 20: 460-465.

Peters M, Fritz P, Bufe A. A bioassay for determination of lipopolysaccharide in environmental samples. Innate Immunity 2012; 18:694-99.

International patent application No. PCT/EP2016/079189

Method for synthetically producing arabinogalactan compounds derived from plants and uses of said compounds for the prophylaxis of allergic reactions.

Applicants: Protectimmun GmbH, Ruhr-Universität Bochum, Forschungszentrum Borstel, Universität Rostock.

Inventors: Peters M, Holst O, Vogel C, Voss A

 

International patent application No. PCT/EP2010/004418

Lipopeptides for treatment and prophylaxis of allergic disease.

Applicants: EMCmicrocollections GmbH, Ruhr-Universität Bochum

Inventors: Peters M, Bufe A, Voss S, Wiesmüller KH.

 

International patent application No. PCT/EP2009/005911

Pharmaceutical composition for prevention and treatment of allergic and/or inflammatory diseases.

Applicants: Protectimmun GmbH, Ruhr-Universität Bochum, Forschungszentrum Borstel

Inventors: Peters M, Kauth M, Bufe A, Holst O.