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Role of epigenetic regulation and inflammasome in epithelial barrier in asthma and atopic dermatitis

English title Role of epigenetic regulation and inflammasome in epithelial barrier in asthma and atopic dermatitis
Applicant Akdis Cezmi
Number 176190
Funding scheme Project funding (Div. I-III)
Research institution Schweizerisches Institut für Allergie- und Asthmaforschung
Institution of higher education Swiss Institute of Allergy and Asthma Research - SIAF
Main discipline Immunology, Immunopathology
Start/End 01.10.2017 - 30.09.2021
Approved amount 632'000.00
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Keywords (10)

Asthma; Epithelial cells; Innate immune response; Inflammasome; Epigenetic; Cytokines; Tight Junctions; T cells; Atopic dermatitis; Barrier

Lay Summary (German)

Lead
Mit einem epidemischen Anstieg in den letzten 60 Jahren, betreffen allergische Erkrankungen über 1 Mrd. Menschen weltweit, mit steigender Prävalenz auf 4 Mrd. bis 2050.
Lay summary

In der Schweiz leiden rund 1.7 Mio. Menschen an einer allergischen Krankheit. Ca. 5-10% dieser Krankheiten mit schwerer Form können zum Tode führen. Wir konnten zusammen mit anderen beweisen, dass Defekte in der Epithelbarriere der Tight Junctions eine wichtige Rolle in der Pathogenese dieser Krankheiten spielt. Man hat zeigen können, dass die Barrierefunktion von Lungenepithelzellen von Asthmatikern, von Epithelzellen in Stirn- sowie Nebenhöhlen bei Patienten mit chronischer Rhinosinusitis und von Hautzellen bei atopischer Dermatitis beschädigt und undicht ist. Allergene, bakterielle Toxine und andere Stoffe können so das undichte Epithel durchdringen und dort womöglich die Abwehrzellen aktivieren und zu schwerer chronischer Entzündung führen. Diese Studie konzentriert sich auf die Regulierung der Epithelbarriere und ihre zellulären sowie molekularen Mechanismen. Die Untersuchungen werden parallel bei Asthma und atopischer Dermatitis geführt und konzentrieren sich besonders auf in vivo relevante Erkenntnisse, die aus primären humanen Zellen und Biopsien sowie aus Mausmodellen gewonnen werden. Oberstes Ziel dieser Studie ist, neue Wege für Prävention und Behandlung von Asthma und atopischer Dermatitis, um die individuelle Belastung der Patienten und ihrer Familien zu mindern. Diese beiden allergischen Erkrankungen betreffen fast die Hälfte der Bevölkerung weltweit und verursachen sehr hohe Gesundheitskosten. Diese Studie wird einen weiterreichenden Einfluss auch auf andere Disziplinen der Human- und Tiermedizin haben.

 

Direct link to Lay Summary Last update: 05.10.2017

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
EAACI Research and Outreach Committee: Improving standards and facilitating global collaboration through a Research Excellence Network
Shamji Mohamed H., Akdis Cezmi A., Barber Domingo, Canonica Walter, Chivato Tomás, Giacco Stefano, Hoffman‐Sommergruber Karin, Jutel Marek, Knol Edward, Ollert Markus, O'Mahony Liam, Palomares Oscar, Sastre Joaquin, Schwarze Jürgen, Smolinska Sylwia, Vieths Stefan, Agache Ioana (2020), EAACI Research and Outreach Committee: Improving standards and facilitating global collaboration through a Research Excellence Network, in Allergy, 75(8), 1899-1901.
Atopic dermatitis in a cohort of West Highland white terriers in Switzerland. Part II: estimates of early life factors and heritability
Rostaher Ana, Dolf Gaudenz, Fischer Nina Maria, Silaghi Cornelia, Akdis Cezmi, Zwickl Lena, Audergon Sabrina, Favrot Claude (2020), Atopic dermatitis in a cohort of West Highland white terriers in Switzerland. Part II: estimates of early life factors and heritability, in Veterinary Dermatology, 31(4), 276-276.
Enhancing Data Reliability in TOMAHAQ for Large‐Scale Protein Quantification
Liu Fang, Singhal Kratika, Matney Rowan, Acharya Swati, Akdis Cezmi A., Nadeau Kari C., Chien Allis S., Leib Ryan D. (2020), Enhancing Data Reliability in TOMAHAQ for Large‐Scale Protein Quantification, in PROTEOMICS, 20(11), 1900105-1900105.
Recent developments and advances in atopic dermatitis and food allergy
Sugita Kazunari, Akdis Cezmi A. (2020), Recent developments and advances in atopic dermatitis and food allergy, in Allergology International, 69(2), 204-214.
Skin barrier damage after exposure to paraphenylenediamine
Meisser Sanne S., Altunbulakli Can, Bandier Josefine, Opstrup Morten S., Castro-Giner Francesc, Akdis Mübeccel, Bonefeld Charlotte M., Johansen Jeanne D., Akdis Cezmi A. (2020), Skin barrier damage after exposure to paraphenylenediamine, in Journal of Allergy and Clinical Immunology, 145(2), 619-631.e2.
Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients
Michalovich David, Rodriguez-Perez Noelia, Smolinska Sylwia, Pirozynski Michal, Mayhew David, Uddin Sorif, Van Horn Stephanie, Sokolowska Milena, Altunbulakli Can, Eljaszewicz Andrzej, Pugin Benoit, Barcik Weronika, Kurnik-Lucka Magdalena, Saunders Ken A., Simpson Karen D., Schmid-Grendelmeier Peter, Ferstl Ruth, Frei Remo, Sievi Noriane, Kohler Malcolm, Gajdanowicz Pawel, Graversen Katrine B., Lindholm Bøgh Katrine, Jutel Marek, et al. (2019), Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients, in Nature Communications, 10(1), 5711-5711.
Direct assessment of skin epithelial barrier by electrical impedance spectroscopy
Rinaldi Arturo O., Morita Hideaki, Wawrzyniak Paulina, Dreher Anita, Grant Simon, Svedenhag Per, Akdis Cezmi A. (2019), Direct assessment of skin epithelial barrier by electrical impedance spectroscopy, in Allergy, 74(10), 1934-1944.
Immunological methods for diagnosis and monitoring of IgE‐mediated allergy caused by industrial sensitizing agents (IMExAllergy)
Baur Xaver, Akdis Cezmi A., Budnik Lygia Therese, Cruz Maria Jesus, Fischer Axel, Förster‐Ruhrmann Ulrike, Göen Thomas, Goksel Ozlem, Heutelbeck Astrid R., Jones Meinir, Lux Harald, Maestrelli Piero, Munoz Xavier, Nemery Benoit, Schlünssen Vivi, Sigsgaard Torben, Traidl‐Hoffmann Claudia, Siegel Paul (2019), Immunological methods for diagnosis and monitoring of IgE‐mediated allergy caused by industrial sensitizing agents (IMExAllergy), in Allergy, 74(10), 1885-1897.
Acute Respiratory Barrier Disruption by Ozone Exposure in Mice
Sokolowska Milena, Quesniaux Valerie F. J., Akdis Cezmi A., Chung Kian Fan, Ryffel Bernhard, Togbe Dieudonnée (2019), Acute Respiratory Barrier Disruption by Ozone Exposure in Mice, in Frontiers in Immunology, 10, 1664-3224.
miR‐10a‐5p is increased in atopic dermatitis and has capacity to inhibit keratinocyte proliferation
Vaher Helen, Runnel Toomas, Urgard Egon, Aab Alar, Carreras Badosa Gemma, Maslovskaja Julia, Abram Kristi, Raam Liisi, Kaldvee Bret, Annilo Tarmo, Tkaczyk Eric R., Maimets Toivo, Akdis Cezmi A., Kingo Külli, Rebane Ana (2019), miR‐10a‐5p is increased in atopic dermatitis and has capacity to inhibit keratinocyte proliferation, in Allergy, 74(11), 2146-2156.
Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care
Breiteneder Heimo, Diamant Zuzana, Eiwegger Thomas, Fokkens Wytske J., Traidl‐Hoffmann Claudia, Nadeau Kari, O’Hehir Robyn E., O’Mahony Liam, Pfaar Oliver, Torres Maria J., Wang De Yun, Zhang Luo, Akdis Cezmi A. (2019), Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care, in Allergy, 74(12), 2293-2311.
Gene expression signatures of circulating human type 1, 2, and 3 innate lymphoid cells
Li Shuo, Morita Hideaki, Sokolowska Milena, Tan Ge, Boonpiyathad Tadech, Opitz Lennart, Orimo Keisuke, Archer Stuart K., Jansen Kirstin, Tang Mimi L.K., Purcell Damian, Plebanski Magdalena, Akdis Cezmi A. (2019), Gene expression signatures of circulating human type 1, 2, and 3 innate lymphoid cells, in Journal of Allergy and Clinical Immunology, 143(6), 2321-2325.
Human bocaviruses and paediatric infections
Christensen Andreas, Kesti Olli, Elenius Varpu, Eskola Anna L, Døllner Henrik, Altunbulakli Can, Akdis Cezmi A, Söderlund-Venermo Maria, Jartti Tuomas (2019), Human bocaviruses and paediatric infections, in The Lancet Child & Adolescent Health, 3(6), 418-426.
Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid
Morita Hideaki, Kubo Terufumi, Rückert Beate, Ravindran Avinash, Soyka Michael B., Rinaldi Arturo Ottavio, Sugita Kazunari, Wawrzyniak Marcin, Wawrzyniak Paulina, Motomura Kenichiro, Tamari Masato, Orimo Keisuke, Okada Naoko, Arae Ken, Saito Kyoko, Altunbulakli Can, Castro-Giner Francesc, Tan Ge, Neumann Avidan, Sudo Katsuko, O'Mahony Liam, Honda Kenya, Nakae Susumu, Saito Hirohisa, et al. (2019), Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid, in Journal of Allergy and Clinical Immunology, 143(6), 2190-2201.e9.
Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells
Wang Ming, Tan Ge, Eljaszewicz Andrzej, Meng Yifan, Wawrzyniak Paulina, Acharya Swati, Altunbulakli Can, Westermann Patrick, Dreher Anita, Yan Liying, Wang Chengshuo, Akdis Mubeccel, Zhang Luo, Nadeau Kari C., Akdis Cezmi A. (2019), Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells, in Journal of Allergy and Clinical Immunology, 143(5), 1892-1903.
Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice
Tan Hern-Tze Tina, Hagner Stefanie, Ruchti Fiorella, Radzikowska Urszula, Tan Ge, Altunbulakli Can, Eljaszewicz Andrzej, Moniuszko Marcin, Akdis Mübeccel, Akdis Cezmi A., Garn Holger, Sokolowska Milena (2019), Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice, in Allergy, 74(2), 294-307.
Bacterial secretion of histamine within the gut influences immune responses within the lung
Barcik Weronika, Pugin Benoit, Brescó Marina Sabaté, Westermann Patrick, Rinaldi Arturo, Groeger David, Van Elst Dries, Sokolowska Milena, Krawczyk Krzysztof, Frei Remo, Ferstl Ruth, Wawrzyniak Marcin, Altunbulakli Can, Akdis Cezmi A., O'Mahony Liam (2019), Bacterial secretion of histamine within the gut influences immune responses within the lung, in Allergy, 74(5), 899-909.
Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis
Mikola Emilia, Elenius Varpu, Saarinen Maria, Palomares Oscar, Waris Matti, Turunen Riitta, Puhakka Tuomo, Ivaska Lotta, Rückert Beate, Aab Alar, Vahlberg Tero, Vuorinen Tytti, Allander Tobias, Camargo Carlos A., Akdis Mübeccel, Akdis Cezmi A., Jartti Tuomas (2018), Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis, in Clinical and Translational Allergy, 8(1), 22-22.
High levels of butyrate and propionate in early life are associated with protection against atopy
Roduit Caroline, Frei Remo, Ferstl Ruth, Loeliger Susanne, Westermann Patrick, Rhyner Claudio, Schiavi Elisa, Barcik Weronika, Rodriguez‐Perez Noelia, Wawrzyniak Marcin, Chassard Christophe, Lacroix Christophe, Schmausser‐Hechfellner Elisabeth, Depner Martin, Mutius Erika, Braun‐Fahrländer Charlotte, Karvonen Anne M., Kirjavainen Pirkka V., Pekkanen Juha, Dalphin Jean‐Charles, Riedler Josef, Akdis Cezmi, Lauener Roger, O'Mahony Liam, et al. (2018), High levels of butyrate and propionate in early life are associated with protection against atopy, in Allergy, 74(4), 799-809.
Relations between epidermal barrier dysregulation and Staphylococcus species–dominated microbiome dysbiosis in patients with atopic dermatitis
Altunbulakli Can, Reiger Matthias, Neumann Avidan U., Garzorz-Stark Natalie, Fleming Megan, Huelpuesch Claudia, Castro-Giner Francesc, Eyerich Kilian, Akdis Cezmi A., Traidl-Hoffmann Claudia (2018), Relations between epidermal barrier dysregulation and Staphylococcus species–dominated microbiome dysbiosis in patients with atopic dermatitis, in Journal of Allergy and Clinical Immunology, 142(5), 1643-1647.e12.
Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33
Michaudel Chloé, Mackowiak Claire, Maillet Isabelle, Fauconnier Louis, Akdis Cezmi A., Sokolowska Milena, Dreher Anita, Tan Hern-Tze Tina, Quesniaux Valérie F., Ryffel Bernhard, Togbe Dieudonnée (2018), Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33, in Journal of Allergy and Clinical Immunology, 142(3), 942-958.
Staphylococcus aureus enhances the tight junction barrier integrity in healthy nasal tissue, but not in nasal polyps
Altunbulakli Can, Costa Rita, Lan Feng, Zhang Nan, Akdis Mubeccel, Bachert Claus, Akdis Cezmi A. (2018), Staphylococcus aureus enhances the tight junction barrier integrity in healthy nasal tissue, but not in nasal polyps, in Journal of Allergy and Clinical Immunology, 142(2), 665-668.e8.
Human CD40 ligand–expressing type 3 innate lymphoid cells induce IL-10–producing immature transitional regulatory B cells
Komlósi Zsolt I., Kovács Nóra, van de Veen Willem, Kirsch Anna Isabella, Fahrner Heinz Benedikt, Wawrzyniak Marcin, Rebane Ana, Stanic Barbara, Palomares Oscar, Rückert Beate, Menz Günter, Akdis Mübeccel, Losonczy György, Akdis Cezmi A. (2018), Human CD40 ligand–expressing type 3 innate lymphoid cells induce IL-10–producing immature transitional regulatory B cells, in Journal of Allergy and Clinical Immunology, 142(1), 178-194.e11.
Transforming growth factor-β1 decreases epithelial tight junction integrity in chronic rhinosinusitis with nasal polyps
Jiao Jian, Wang Ming, Duan Su, Meng Yifan, Meng Na, Li Ying, Fan Erzhong, Akdis Cezmi A., Zhang Luo (2018), Transforming growth factor-β1 decreases epithelial tight junction integrity in chronic rhinosinusitis with nasal polyps, in Journal of Allergy and Clinical Immunology, 141(3), 1160-1163.e9.
A Fluorescent Probe to Unravel Functional Features of Cannabinoid Receptor CB 1 in Human Blood and Tonsil Immune System Cells
Martín-Fontecha Mar, Angelina Alba, Rückert Beate, Rueda-Zubiaurre Ainoa, Martín-Cruz Leticia, van de Veen Willem, Akdis Mübeccel, Ortega-Gutiérrez Silvia, López-Rodríguez María Luz, Akdis Cezmi A., Palomares Oscar (2018), A Fluorescent Probe to Unravel Functional Features of Cannabinoid Receptor CB 1 in Human Blood and Tonsil Immune System Cells, in Bioconjugate Chemistry, 29(2), 382-389.
Monitoring inflammatory heterogeneity with multiple biomarkers for multidimensional endotyping of asthma
Agache Ioana, Strasser Daniel S., Pierlot Gabin M., Farine Hervé, Izuhara Kenji, Akdis Cezmi A. (2018), Monitoring inflammatory heterogeneity with multiple biomarkers for multidimensional endotyping of asthma, in Journal of Allergy and Clinical Immunology, 141(1), 442-445.
Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients
Sugita Kazunari, Steer Catherine A., Martinez-Gonzalez Itziar, Altunbulakli Can, Morita Hideaki, Castro-Giner Francesc, Kubo Terufumi, Wawrzyniak Paulina, Rückert Beate, Sudo Katsuko, Nakae Susumu, Matsumoto Kenji, O'Mahony Liam, Akdis Mübeccel, Takei Fumio, Akdis Cezmi A. (2018), Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients, in Journal of Allergy and Clinical Immunology, 141(1), 300-310.e11.
Immune regulation by histamine and histamine-secreting bacteria
Barcik Weronika, Wawrzyniak Marcin, Akdis Cezmi A, O’Mahony Liam (2017), Immune regulation by histamine and histamine-secreting bacteria, in Current Opinion in Immunology, 48, 108-113.
miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis
Hermann Helen, Runnel Toomas, Aab Alar, Baurecht Hansjörg, Rodriguez Elke, Magilnick Nathaniel, Urgard Egon, Šahmatova Liisi, Prans Ele, Maslovskaja Julia, Abram Kristi, Karelson Maire, Kaldvee Bret, Reemann Paula, Haljasorg Uku, Rückert Beate, Wawrzyniak Paulina, Weichenthal Michael, Mrowietz Ulrich, Franke Andre, Gieger Christian, Barker Jonathan, Trembath Richard, Tsoi Lam C., et al. (2017), miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis, in Journal of Investigative Dermatology, 137(9), 1945-1954.
The Journal of Allergy and Clinical Immunology : An update on style and substance
Akdis Cezmi A., Byrne Justin, Ballas Zuhair K. (2017), The Journal of Allergy and Clinical Immunology : An update on style and substance, in Journal of Allergy and Clinical Immunology, 140(1), 60-62.

Collaboration

Group / person Country
Types of collaboration
Brecht Stelant, Department of , Allergy and Clinical Immunology, KU Leuven Belgium (Europe)
- Publication
- Exchange of personnel
Fumio Takei, Department of Pathology and Laboratory Medicine, University of British Columbia Canada (North America)
- Publication
Hideaki Morita, Department of Allergy and Clinical Immunology National Research Institute Tokyo Japan (Asia)
- Publication
- Exchange of personnel
Claudia Traidl-Hoffmann, Institute of Environmental Medicine, UNIKA-T, Ausburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Kazunari Sugita, Division of Dermatology, Department of Medicine Totori University, Yonago Japan (Asia)
- Publication
- Research Infrastructure
Ioana Agache, Transylvania University Brasov Romania Romania (Europe)
- Publication
- Exchange of personnel
Michael Soyka, Department of Otorhinolaryngology, Head and Neck Surgery, University Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Peter Schmid-Grendelmeier, Allergy Station, University Zurich Switzerland (Europe)
- Publication
- Research Infrastructure
- Exchange of personnel
Kari Nadeau, SEAN Parker Asthma and Allergy Center, Stanford University United States of America (North America)
- Publication
- Research Infrastructure
Paulina Wawrzyniak, Children's Research Center, University Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events



Self-organised

Title Date Place
World Immune Regulation Meeting XIII 06.04.2019 Davos, Switzerland
World Immune Regulation Meeting XII 14.03.2018 Davos, Switzerland

Knowledge transfer events



Self-organised

Title Date Place
World Immune Regulation Meeting XIII 06.04.2019 Davos, Switzerland
World Immune Regulation Meeting XII 17.03.2018 Davos, Switzerland

Awards

Title Year
Cantonal Recognition Prize, Canton of Grissons 2020
Honorary Professor, Wuhan University, China 2020
Fellow of the European Academy of Allergy and Clinical Immunology 2019
Honorary Member of the European Academy of Allergy and Clinical Immunology 2019
Robert W. Goltz Lecture, Minneapolis University, 2019 2019
Honorary Member, Swiss Society of Allergy and Clinical Immunology 2018
AAAAI In-training Member International Travel Grant Scholarship. AAAAI annual meeting, Atlanta GA, USA, 3-6 March 2017. 2017
European Respiratory Society Long-term Fellowship Award, extension 01.10.2016-31.03.2017. 2017

Patents

Title Date Number Inventor Owner
A skin barrier detection method by using skin 05.11.2018 PCT/EP2019/078227

Associated projects

Number Title Start Funding scheme
156823 Dysregulated epithelial barrier function in asthma 01.10.2014 Project funding (Div. I-III)

Abstract

Burden of Allergic Diseases: With an epidemic rise during the last 60 years, allergic diseases are affecting the lives of more than one billion people worldwide, and their prevalence is expected to reach up to 4 billion in 2050. Currently, 300 million people (4.2%) suffer from asthma, 500 million (6.5%) from atopic dermatitis (AD), 900 million (12 %) from allergic rhinitis) and 700 million (9%) from food allergy worldwide. The prevalence of these four allergic diseases is approximately 1.7 million 22% in Switzerland. Atopic dermatitis is the most prevalent chronic disease in childhood. Asthma represents one of the highest costs to health care system. Allergic rhinitis is the number one disease for job absenteeism (missing work days) and presenteeism (being on the job, but not fully functioning because of disease). Approximately, 5-10% of all of these diseases present with severe forms and can cause deaths. It was recently shown by us and others that epithelial tight junction barrier defect plays an important role in the pathogenesis of these diseases.Epithelial barrier function: of asthmatic bronchial epithelial cells, sinus epithelial cells in chronic rhinosinusitis and skin keratinocytes in atopic dermatitis have been demonstrated to be defective and leaky. Allergens, bacterial toxins and other particles are able to penetrate the leaky epithelium, where they may activate the immune system cells leading to severe chronic inflammation. Epithelial tight junctions (TJ) are responsible for the regulation of paracellular flux and epithelial impermeability and can be considered as gatekeepers that could contribute both to aggravation of inflammation-related tissue damage or resolution of inflammation via drainage towards out side of the affected tissues. This study focuses on the regulation of particularly TJ barrier by epigenetic mechanisms and inflammasome.Planned experiments: According to our strong preliminary data, we hypothesize here that “epithelial tight junction barrier is epigenetically controlled” and “epithelial barrier leakiness is affected by inflammasome and both TJ barrier and inflammasome are epigenetically regulated”. We will perform this research in asthma and atopic dermatitis in parallel and particularly focus on in vivo relevant findings that will be obtained from direct human primary cells and biopsies as well as mouse models. We aim to demonstrate epigenetic mechanisms of bronchial and skin epithelial barrier leakiness in different endotypes and phenotypes of asthma and atopic dermatitis and bring a new perspective from bench to patient side. We will use several important and in vivo relevant stimulants to study the “barrier”, “epigenetics” and “inflammasome” triangle. They will be house dust mite, human rhinovirus, commercial detergents and their surfactants, and CpG oligonucleotides. In this way, we will be able to investigate barrier damaging and recovering as well as inflammasome-activating and -nonactivating stimulants.Impact and innovative potential: The ultimate aim of this research is to find out novel preventive and treatment ways for two major allergic diseases, asthma and atopic dermatitis to decrease the individual burden of the patients and their families, which affects almost half of the World’s population and extremely high health care costs. Our research includes disease endo and phenotyping concepts and opens a new window for a precision medicine approach to barrier leakiness, such as the establishment of leaky barrier endotype. Many aspects of this research will find broader impact in other disciplines of human and veterinary medicine, because similar mechanisms of epithelial barrier dysregulation play roles in other diseases such as chronic rhinosinusitis, COPD and inflammatory bowel disease. In addition, epigenetic regulation of inflammasome activation thresholds has a link to essentially all inflammatory diseases.
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