Visual Universitätsmedizin Mainz

Head:

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Prof. Dr. med. Joachim Saloga
Tel: +49-6131-173751
Fax: +49-6131-17473751
E-Mail:  joachim.saloga@unimedizin-mainz.de

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PD Dr. rer. nat. Iris Bellinghausen
Tel: +49-6131-172238
Fax: +49-6131-175505
E-Mail:  iris.bellinghausen@unimedizin-mainz.de

Scientists:

M.Sc. Robert Ose, PhD Student
Tel: +49-6131-172238
E-Mail:  roberose@uni-mainz.de

M.Sc. Johannes Ewald, PhD Student
Tel: +49-6131-172238
E-Mail:  jewald@students.uni-mainz.de

Jessica Tu, MD Student
Tel: +49-6131-172238
E-Mail:  jessicatu91@gmail.com

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Research Interests

The major research interests of our group are the analysis of IgE-mediated allergies of the immediate type and their inhibition by tolerogenic dendritic cells and regulatory T cells. Additionally, we investigate the allergic immune response before and after allergen-specific immunotherapy (AIT) and we analyze a possible improvement of AIT by encapsulation of allergens in nanoparticle.

Projects:

Modulation of allergen-induced lung and gut inflammation by nutritional wheat amylase trypsin inhibitors (ATIs), activators of the innate immune system, funded by the Deutsche Forschungsgemeinschaft (DFG Project BE 4504/3-1, 2017-2020)

Amylase trypsin inhibitors (ATIs), a family of water soluble non-gluten proteins that are found in wheat and related cereals, have been identified by the AG Schuppan from the Institute of Translational Immunology in Mainz as common nutritional activators of myeloid innate immune cells via engagement of toll-like receptor 4 (TLR4). Furthermore, ATIs have been shown to serve as adjuvants in experimental intestinal inflammatory diseases. In this project we aim to analyze in cooperation with AG Schuppan whether ATIs are also modifiers of allergic inflammation (rhinitis, asthma, food allergy) using different in vitro and in vivo allergy models. Furthermore, we will analyze the modulating effect of the surrounding microbiota. New insights deriving from these experiments will be helpful to clarify the role of nutritional ATIs which are major components in our daily, cereal-based diets as modulators of allergy, and thereby lay the foundation for nutritional intervention studies in patients.


Modulation of allergic immune responses in an established humanized mouse model
, funded by the Deutsche Forschungsgemeinschaft (DFG Project BE 4504/2-1 and 4504/2-2, 2010-2016)

Nowadays, more than 25 % of the population in industrial countries are affected by immediate-type hypersensitivity reactions mediated by IgE such as allergy rhinitis, asthma and atopic eczema. Due to intensive research on basis of in vitro studies with human immune cells and different murine in vivo models of allergy fundamental mechanisms of allergic type I reactions have been elucidated within the last years. However, findings from human in vitro studies are restricted and the immune system of humans and mice differs in several aspects so that the transferability of experimental results from mice to men is limited. New models such as humanized mice are necessary to analyze the interaction of human immune cells under as far as possible physiological conditions particularly to test new therapeutic strategies. During the first period of this project a humanized mouse model of allergy could be established by injection of human cells of allergic donors in immunodeficient mice resulting in the detection of an allergen-induced gut and lung inflammation. In this model, novel therapeutic approaches have been investigated later on. That includes the immunomodulation by regulatory T cells and tolerogenic dendritic cells and the improvement of allergen-specific immunotherapy by combination of allergens and adjuvants such as CpG oligonucleotides or lipopolysaccharides. Additionally, the employment of the humanized mouse model in relation to gut inflammation in celiac disease was analyzed.


Degradable poly(ethylene glycol) (PEG)-nanoparticles for encapsulation of therapeutic proteins, directed transport and controlled release, funded by NMFZ, Max Planck Graduate Center and Graduate School Materials Science in Mainz (2011-2016), proposal for intermural research funding „Analysis of therapeutic use of PEG-Nanoparticles in murine allergy models“ submitted in January 2017, DFG proposal „PEG-nanoparticles for immunotherapy of type I allergies“ to be submitted

Allergen-specific immunotherapy (AIT) is the only available cause-oriented therapy for IgE-mediated allergic diseases such as allergic rhinitis and asthma bronchiale. Successful AIT is characterized by a shift from a Th2/Th17 towards a Th1 immune response and the induction of regulatory T cells leading to immunologic tolerance. Although effectiveness of AIT was confirmed in many clinical trials, it still suffers from drawbacks such as the long-lasting procedure, and in a few cases severe adverse effects like anaphylactic reactions. To reduce this risk, encapsulation of allergens into nanoparticles (NP) and thereby the shielding of the allergen from detection by the immune system might be an attractive approach. In cooperation with the AG Frey from the Institute of Organic Chemistry in Mainz allergens were encapsulated into Polyethylenglykol (PEG)-macromonomers which contain cleavable acetal units allowing a controlled release into the lysosomes of dendritic cells (DC). In preliminary in vitro studies we could show that activation of basophilic leucocytes from the blood of allergic donors with these allergen-encapsulated NP was strongly reduced in comparison to the non-encapsulated free allergen. However, internalization of the NP by DC and induction of allergen-specific T cell proliferation and cytokine production was also lower than that induced by the free allergen. Therefore, we aim to improve encapsulation efficiency and allergen uptake in future studies. Furthermore, the therapeutic use of allergen-encapsulated NP will be analyzed in different mouse models of allergy.

Publications of the last 5 years:

1. Ose R, Tu J, Schink A, Maxeiner J, Schuster P, Lucas K, Saloga J, Bellinghausen I. Cinnamon extract inhibits allergen-specific immune responses in human and murine allergy models. Clin Exp Allergy 2020; 50:41-50

2. Neumann J, Ziegler K, Gelléri M, Fröhlich-Nowoisky J, Liu F, Bellinghausen I, Schuppan D, Birk U, Pöschl U, Cremer C, Lucas K. Nanoscale distribution of TLR4 on primary human macrophages stimulated with LPS and ATI. Nanoscale 2019; 11:9769-79

3. Ziegler K, Neumann J, Liu F, Fröhlich-Nowoisky J, Cremer C, Saloga J, Reinmuth-Selzle K, Pöschl U, Schuppan D, Bellinghausen I*, Lucas K*. Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential in vitro. Front Immunol 2019; 9:3174

4. Seutter von Loetzen C, Reuter A, Spiric J, Schulenborg T, Bellinghausen I, Völker E, Vogel L, Rösch P, Schiller D. Quality and potency profile of eight recombinant isoallergens, largely mimicking total Bet v 1-specific IgE binding of birch pollen. Clin Exp Allergy 2019; 49:712-23

5. Wegner J, Saloga J, Grabbe S, Wilden S, Vewinger N, Lutz J, Weinmann-Menke J, von Stebut E. IgE-specific immunoadsorption: New treatment option for severe refractory atopic dermatitis. Allergy 2019; 74:1190-3

6. Bellinghausen I, Weigmann B, Zevallos V, Maxeiner J, Reissig S, Waisman A, Schuppan D, Saloga J. Wheat amylase/trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice. J Allergy Clin Immunol 2019; 143:201-12

7. Bradfisch F, Pietsch M,  Forchhammer S, Strobl S, Stege HM, Pietsch R, Carstens S, Schäkel K, Yazdi A, Saloga J. Anaphylaktische Reaktionen nach Tollwutimpfungen mit Sensibilisierung gegenüber Gelatine. Allergo J Int 2019; 28: 103-6

8. Klimek L, Bachert C, Pfaar O, Becker S, Bieber T, Brehler R, Buhl R, Casper I, Chaker A, Czech W, Fischer J, Fuchs T, Gerstlauer M, Hörmann K, Jakob T, Jung K, Kopp MV, Mahler V, Merk H, Mülleneisen N, Nemat K, Rabe U, Ring J, Saloga J, Schlenter W, Schmidt-Weber C, Schwalfenberg A, Seyfarth H, Sperl A, Spindler T, Staubach P, Strieth S, Treudler R, Vogelberg C, Wallrafen A, Wehrmann W, Wrede H, Zuberbier T, Bedbrook A, Canonica GW, Cardona V, Casale T, Czarlewski W, Fokkens WJ, Hamelmann E, Hellings PW, Jutel M, Larenas-Linnemann D, Mullol J, Papadopoulos NG, Toppila-Salmi S, Werfel T, Bousquet CJ. ARIA Leitlinie 2019: Behandlung der allergischen Rhinitis im deutschen Gesundheitssystem. Allergo J Int 2019; 28:255-76

9. Lang-Yona N, Kunert AT, Vogel L, Kampf CJ, Bellinghausen I, Saloga J, Schink A, Ziegler K, Lucas K, Schuppan D, Pöschl U, Weber B, Fröhlich-Nowoisky J. Fresh water, marine and terrestrial cyanobacteria display distinct allergen characteristics. Sci Total Environ 2018; 612:767-74

10. Jappe U, Minge S, Kreft B, Ludwig A, Przybilla B, Walker A, Varga R, Seidel P, Biedermann T, Anemüller W, Kromminga A, Ruëff F, Merk H, Wagner N, Treudler R, Worm M, Waldmann I, Saloga J, Becker WM, Goldmann T, Platts-Mills TA, Homann A. Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling. Allergy 2018; 73:93-105

11. Pohlit H, Bellinghausen I, Frey H, Saloga J. Recent advances in the use of nanoparticles for allergen-specific immunotherapy. Allergy 2017; 72:1461-74

12. Pohlit H, Leibig D. Frey H. Poly(Ethylene Glycol) Dimethacrylates with Cleavable Ketal Sites: Precursors for Cleavable PEG-Hydrogels. Macromol Biosci. 2017; doi:10.1002/mabi.201600532

13. Reinmuth-Selzle K, Kampf CJ, Lucas K, Lang-Yona N, Fröhlich-Nowoisky J, Shiraiwa M, Lakey PSJ, Lai S, Liu F, Kunert AT, Ziegler K, Shen F, Sgarbanti R, Weber B, Bellinghausen I, Saloga J, Weller MG, Duschl A, Schuppan D, Pöschl U. Air Pollution and Climate Change Effects on Allergies in the Anthropocene: Abundance, Interaction, and Modification of Allergens and Adjuvants. Environ Sci Technol 2017; 51:4119-41

14. Treudler R, Franke A, Schmiedeknecht A, Ballmer-Weber B, Worm M, Werfel T, Jappe U, Biedermann T, Schmitt J, Brehler R, Kleinheinz A, Kleine-Tebbe J, Brüning H, Ruëff F, Ring J, Saloga J, Schäkel K, Holzhauser T, Vieths S, Simon JC. BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy. Allergy 2017; 72:1243-53

15. Treudler R, Franke A, Schmiedeknecht A, Ballmer-Weber BK, Worm M, Werfel T, Jappe U, Biedermann T, Schmitt J, Brehler R, Kleinheinz A, Kleine-Tebbe J, Brüning H, Ruëff F, Ring J, Saloga J, Schäkel K, Holzhauser T, Vieths S, Simon JC. Standardization of double blind placebo controlled food challenge with soy within a multicentre trial. Clin Transl Allergy 2016; 6:39

16. Trojandt S, Bellinghausen I, Reske-Kunz AB, Bros M. Tumor-derived immuno-modulators induce overlapping pro-tolerogenic gene expression signatures in human dendritic cells. Hum Immunol 2016; 77:1223-31

17. Bellinghausen I, Saloga J. Analysis of allergic immune responses in humanized mice. Cell Immunol 2016; 308:7-12

18. Pohlit H, Frey H, Saloga J. Could allergen-specific immunotherapy benefit from the use of nanocarriers? Nanomedicine 2016; 11:1329-31

19. Herzberger J, Niederer K, Pohlit H, Seiwert J, Worm M, Wurm FR, Frey H. Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation. Chem Rev 2016; 116:2170-243

20. Hahn SA, Bellinghausen I, Trinschek B, Becker C. Translating Treg Therapy in Humanized Mice. Front Immunol 2015; 6: 623

21. Pohlit H, Bellinghausen I, Schömer M, Heydenreich B, Saloga J, Frey H. Biodegradable pH-Sensitive Poly(ethylene glycol) Nanocarriers for Allergen Encapsulation and Controlled Release. Biomacromolecules 2015; 16:3103-11

22. Husslik F, Hanschmann KM, Krämer A, Seutter von Loetzen C, Schweimer K, Bellinghausen I, Treudler R, Simon JC, Vogel L, Völker E, Randow S, Reuter A, Rösch P, Vieths S, Holzhauser T, Schiller D. Folded or Not? Tracking Bet v 1 Conformation in Recombinant Allergen Preparations. PLoS One 2015; 10:e0132956

23. Eschborn M, Weigmann B, Reissig S, Waisman A, Saloga J, Bellinghausen I. Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice. J Allergy Clin Immunol 2015; 136:159-68

24. Jaeckels N, Bellinghausen I, Fronk P, Heydenreich B, Saloga J, Decker H. Assessment of sensitization to grape and wine allergens as possible causes of adverse reactions to wine: a pilot study. Clin Transl Allergy 2015;5:21. doi: 10.1186/s13601-015-0065-8. eCollection 2015

25. Ulges A, Klein M, Reuter S, Gerlitzki B, Hoffmann M, Grebe N, Staudt V, Stergiou N, Bohn T, Brühl TJ, Muth S, Yurugi H, Rajalingam K, Bellinghausen I, Tuettenberg A, Hahn S, Reißig S, Haben I, Zipp F, Waisman A, Probst HC, Beilhack A, Buchou T, Filhol-Cochet O, Boldyreff B, Breloer M, Jonuleit H, Schild H, Schmitt E, Bopp T. Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo. Nat Immunol 2015; 16:267-75

26. Schweda K, Hainz M, Loquai C, Grabbe S, Saloga J, Tuettenberg A. Prurigo nodularis as index symptom of (non-Hodgkin) lymphoma: ultrasound as a helpful diagnostic tool in dermatological disorders of unknown origin. Int J Dermatol 2015; 54:462-4