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251. Biology and dynamics of B cells in the context of IgE‐mediated food allergy.

Author

Satitsuksanoa, Pattraporn, Daanje, Monique, Akdis, Mübeccel, Boyd, Scott D., and Veen, Willem

Subjects
B cells, FOOD allergy, IMMUNOREGULATION, IMMUNOGLOBULIN class switching, IMMUNOLOGIC memory
Abstract

An increasing number of people suffer from IgE‐mediated food allergies. The immunological mechanisms that cause IgE‐mediated food allergy have been extensively studied. B cells play a key role in the development of IgE‐mediated food allergies through the production of allergen‐specific antibodies. While this particular function of B cells has been known for many years, we still do not fully understand the mechanisms that regulate the induction and maintenance of allergen‐specific IgE production. It is still not fully understood where in the body IgE class switch recombination of food allergen‐specific B cells occurs, and what processes are involved in the immunological memory of allergen‐specific IgE responses. B cells can also contribute to the regulation of allergen‐specific immune responses through other mechanisms such as antigen presentation and cytokine production. Recent technological advances have enabled highly detailed analysis of small subsets of B cells down to the single‐cell level. In this review, we provide an overview of the current knowledge on the biology of B cells in relation to IgE‐mediated food allergies. [ABSTRACT FROM AUTHOR]

Published
2021
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253. Mechanisms of allergen-specific immunotherapy

Author

Fujita Hiroyuki, Soyka Michael B, Akdis Mübeccel, and Akdis Cezmi A

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Allergen-specific immunotherapy (allergen-SIT) is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg) cells and inducible IL-10- and TGF-β-producing type 1 Treg (Tr1) cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro-inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non-inflammatory antibodies particularly IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases.

Published
2012
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255. A fluorescent probe to unravel functional features of cannabinoid receptor CB1 in human blood and tonsil immune system cells

Author

Martín-Fontecha, Mar, Angelina, Alba, Rückert, Beate, Rueda-Zubiaurre, Ainoa, Martin-Cruz, Leticia, van de Veen, Willem, Akdis, Mübeccel, Ortega-Gutierrez, Silvia, López-Rodrí­guez, María L, Akdis, Cezmi A, Palomares, Oscar, University of Zurich, and Palomares, Oscar

Subjects
3004 Pharmacology, 1502 Bioengineering, 10183 Swiss Institute of Allergy and Asthma Research, 1305 Biotechnology, 3003 Pharmaceutical Science, 2204 Biomedical Engineering, 610 Medicine & health, 1605 Organic Chemistry
Published
2018

256. Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells

Author

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, University of Zurich, and Komlósi, Zsolt I

Subjects
2403 Immunology, 10183 Swiss Institute of Allergy and Asthma Research, Immunology, 2723 Immunology and Allergy, Immunology and Allergy, 610 Medicine & health
Published
2018

257. Impaired memory B‐cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper‐IgE syndrome

Author

Veen, Willem, primary, Krätz, Carolin E., additional, McKenzie, Craig I., additional, Aui, Pei M., additional, Neumann, Jens, additional, Noesel, Carel J. M., additional, Wirz, Oliver F., additional, Hagl, Beate, additional, Kröner, Carolin, additional, Spielberger, Benedikt D., additional, Akdis, Cezmi A., additional, Zelm, Menno C., additional, Akdis, Mübeccel, additional, and Renner, Ellen D., additional

Published
2019
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260. Association of Checkpoint Inhibitor–Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non–Small Cell Lung Cancer

Author

Berner, Fiamma, primary, Bomze, David, additional, Diem, Stefan, additional, Ali, Omar Hasan, additional, Fässler, Mirjam, additional, Ring, Sandra, additional, Niederer, Rebekka, additional, Ackermann, Christoph J., additional, Baumgaertner, Petra, additional, Pikor, Natalia, additional, Cruz, Cristina Gil, additional, van de Veen, Willem, additional, Akdis, Mübeccel, additional, Nikolaev, Sergey, additional, Läubli, Heinz, additional, Zippelius, Alfred, additional, Hartmann, Fabienne, additional, Cheng, Hung-Wei, additional, Hönger, Gideon, additional, Recher, Mike, additional, Goldman, Jonathan, additional, Cozzio, Antonio, additional, Früh, Martin, additional, Neefjes, Jacques, additional, Driessen, Christoph, additional, Ludewig, Burkhard, additional, Hegazy, Ahmed N., additional, Jochum, Wolfram, additional, Speiser, Daniel E., additional, and Flatz, Lukas, additional

Published
2019
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262. Der p 1‐specific regulatory T‐cell response during house dust mite allergen immunotherapy

Author

Boonpiyathad, Tadech, primary, Sokolowska, Milena, additional, Morita, Hideaki, additional, Rückert, Beate, additional, Kast, Jeannette I., additional, Wawrzyniak, Marcin, additional, Sangasapaviliya, Atik, additional, Pradubpongsa, Panitan, additional, Fuengthong, Rattanaporn, additional, Thantiworasit, Pattarawat, additional, Sirivichayakul, Sunee, additional, Kwok, William W., additional, Ruxrungtham, Kiat, additional, Akdis, Mübeccel, additional, and Akdis, Cezmi A., additional

Published
2019
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263. Comparison of regulatory B cells in asthma and allergic rhinitis

Author

Wirz, Oliver F., primary, Głobińska, Anna, additional, Ochsner, Urs, additional, van de Veen, Willem, additional, Eller, Esben, additional, Christiansen, Elisabeth S., additional, Halken, Susanne, additional, Nielsen, Christian, additional, Bindslev‐Jensen, Carsten, additional, Antó, Josep M., additional, Bousquet, Jean, additional, Akdis, Cezmi A., additional, and Akdis, Mübeccel, additional

Published
2018
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264. Rhinovirus Species–Specific Antibodies Differentially Reflect Clinical Outcomes in Health and Asthma

Author

Megremis, Spyridon, primary, Niespodziana, Katarzyna, additional, Cabauatan, Clarissa, additional, Xepapadaki, Paraskevi, additional, Kowalski, Marek L., additional, Jartti, Tuomas, additional, Bachert, Claus, additional, Finotto, Susetta, additional, West, Peter, additional, Stamataki, Sofia, additional, Lewandowska-Polak, Anna, additional, Lukkarinen, Heikki, additional, Zhang, Nan, additional, Zimmermann, Theodor, additional, Stolz, Frank, additional, Neubauer, Angela, additional, Akdis, Mübeccel, additional, Andreakos, Evangelos, additional, Valenta, Rudolf, additional, and Papadopoulos, Nikolaos G., additional

Published
2018
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266. Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice

Author

Tan, Hern-Tze Tina, primary, Hagner, Stefanie, additional, Ruchti, Fiorella, additional, Radzikowska, Urszula, additional, Tan, Ge, additional, Altunbulakli, Can, additional, Eljaszewicz, Andrzej, additional, Moniuszko, Marcin, additional, Akdis, Mübeccel, additional, Akdis, Cezmi A., additional, Garn, Holger, additional, and Sokolowska, Milena, additional

Published
2018
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267. Intralymphatic Immunotherapy: Update and Unmet Needs

Author

Senti, Gabriela, primary, Freiburghaus, Andreas U., additional, Larenas-Linnemann, Désirée, additional, Hoffmann, Hans Jürgen, additional, Patterson, Amber M., additional, Klimek, Ludger, additional, Di Bona, Danilo, additional, Pfaar, Oliver, additional, Ahlbeck, Lars, additional, Akdis, Mübeccel, additional, Weinfeld, Dan, additional, Contreras-Verduzco, Francisco A., additional, Pedroza-Melendez, Alvaro, additional, Skaarup, Søren H., additional, Lee, Sang Min, additional, Cardell, Lars-Olaf, additional, Schmid, Johannes M., additional, Westin, Ulla, additional, Dollner, Ralph, additional, and Kündig, Thomas M., additional

Published
2018
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271. Risk factors for severe and critically ill COVID‐19 patients: A review.

Author

Gao, Ya‐dong, Ding, Mei, Dong, Xiang, Zhang, Jin‐jin, Kursat Azkur, Ahmet, Azkur, Dilek, Gan, Hui, Sun, Yuan‐li, Fu, Wei, Li, Wei, Liang, Hui‐ling, Cao, Yi‐yuan, Yan, Qi, Cao, Can, Gao, Hong‐yu, Brüggen, Marie‐Charlotte, Veen, Willem, Sokolowska, Milena, Akdis, Mübeccel, and Akdis, Cezmi A.

Subjects
COVID-19, LYMPHOPENIA, ACUTE kidney failure, TYPE I interferons, CRITICALLY ill, MEDICAL quality control
Abstract

The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19. [ABSTRACT FROM AUTHOR]

Published
2021
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272. Clinical, radiological, and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID‐19 patients.

Author

Zhang, Jin‐jin, Cao, Yi‐yuan, Tan, Ge, Dong, Xiang, Wang, Bin‐chen, Lin, Jun, Yan, You‐qin, Liu, Guang‐hui, Akdis, Mübeccel, Akdis, Cezmi A., and Gao, Ya‐dong

Subjects
COVID-19, LYMPHOPENIA, BLOOD urea nitrogen, HOSPITAL admission & discharge, NEUTROPHILS, ELECTRONIC health records
Abstract

Background: The coronavirus disease 2019 (COVID‐19) has become a global pandemic, with 10%‐20% of severe cases and over 508 000 deaths worldwide. Objective: This study aims to address the risk factors associated with the severity of COVID‐19 patients and the mortality of severe patients. Methods: 289 hospitalized laboratory‐confirmed COVID‐19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials, were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: nonsurvived (n = 49), survived severe (n = 78), and nonsevere (n = 162) groups. Clinical, laboratory, and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low‐dimensional space. Correlations between clinical, radiological, and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay were also collected. Results: Of the 289 patients, the median age was 57 years (range, 22‐88) and 155 (53.4%) patients were male. As of the final follow‐up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leukocyte count, neutrophil count, neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein (CRP), procalcitonin (PCT), D‐dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission, were found in survived severe cases compared to nonsevere cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea, and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from "nonsevere" toward "nonsurvived" via "severe and survived" patients. Strong correlations between the age of patients, the affected lobe numbers, and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay showed that continuing increase of leukocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in‐hospital death. Conclusions: Survived severe and nonsurvived COVID‐19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID‐19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients. [ABSTRACT FROM AUTHOR]

Published
2021
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273. Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis

Author

dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), Frei, Remo, Ferstl, Ruth, Roduit, Caroline, Ziegler, Mario, Schiavi, Elisa, Barcik, Weronika, Rodriguez-Perez, Noelia, Wirz, Oliver F, Wawrzyniak, Marcin, Pugin, Benoit, Nehrbass, Dirk, Jutel, Marek, Smolinska, Sylwia, Konieczna, Patrycja, Bieli, Christian, Loeliger, Susanne, Waser, Marco, Pershagen, Göran, Riedler, Josef, Depner, Martin, Schaub, Bianca, Genuneit, Jon, Renz, Harald, Pekkanen, Juha, Karvonen, Anne M, Dalphin, Jean-Charles, van Hage, Marianne, Doekes, Gert, Akdis, Mübeccel, Braun-Fahrländer, Charlotte, Akdis, Cezmi A, von Mutius, Erika, O'Mahony, Liam, Lauener, Roger P, Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study group, dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), Frei, Remo, Ferstl, Ruth, Roduit, Caroline, Ziegler, Mario, Schiavi, Elisa, Barcik, Weronika, Rodriguez-Perez, Noelia, Wirz, Oliver F, Wawrzyniak, Marcin, Pugin, Benoit, Nehrbass, Dirk, Jutel, Marek, Smolinska, Sylwia, Konieczna, Patrycja, Bieli, Christian, Loeliger, Susanne, Waser, Marco, Pershagen, Göran, Riedler, Josef, Depner, Martin, Schaub, Bianca, Genuneit, Jon, Renz, Harald, Pekkanen, Juha, Karvonen, Anne M, Dalphin, Jean-Charles, van Hage, Marianne, Doekes, Gert, Akdis, Mübeccel, Braun-Fahrländer, Charlotte, Akdis, Cezmi A, von Mutius, Erika, O'Mahony, Liam, Lauener, Roger P, and Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study group

Published
2018

274. Rhinovirus Species–Specific Antibodies Differentially Reflect Clinical Outcomes in Health and Asthma

Author

Megremis, Spyridon, Niespodziana, Katarzyna, Cabauatan, Clarissa, Xepapadaki, Paraskevi, Kowalski, Marek L, Jartti, Tuomas, Bachert, Claus, Finotto, Susetta, West, Peter, Stamataki, Sofia, Lewandowska-Polak, Anna, Lukkarinen, Heikki, Zhang, Nan, Zimmermann, Theodor, Stolz, Frank, Neubauer, Angela, Akdis, Mübeccel, Andreakos, Evangelos, Valenta, Rudolf, Papadopoulos, Nikolaos G, Megremis, Spyridon, Niespodziana, Katarzyna, Cabauatan, Clarissa, Xepapadaki, Paraskevi, Kowalski, Marek L, Jartti, Tuomas, Bachert, Claus, Finotto, Susetta, West, Peter, Stamataki, Sofia, Lewandowska-Polak, Anna, Lukkarinen, Heikki, Zhang, Nan, Zimmermann, Theodor, Stolz, Frank, Neubauer, Angela, Akdis, Mübeccel, Andreakos, Evangelos, Valenta, Rudolf, and Papadopoulos, Nikolaos G

Abstract

RATIONALE: Rhinoviruses are major triggers of common cold and acute asthma exacerbations; Rhinovirus species A, B and C may have distinct clinical impact; however, little is known regarding RV species-specific antibody responses in health and asthma. OBJECTIVES: To describe and compare total and rhinovirus species-specific antibody levels in healthy and asthmatic children, away from an acute event. METHODS: Serum samples from 163 preschool children with mild to moderate asthma and 72 healthy controls from the multinational Predicta cohort were analysed using the recently developed PreDicta rhinovirus antibody chip. MAIN RESULTS: Rhinovirus antibody levels varied, with rhinovirus C and rhinovirus A being higher than rhinovirus B in both groups. Compared to controls, asthma was characterised by significantly higher levels of antibodies to rhinovirus A and rhinovirus C, but not rhinovirus B. Rhinovirus antibody levels positively correlated with the number of common colds over the previous year in healthy children, and wheeze episodes in asthmatics. Antibody levels also positively correlated with asthma severity but not with current asthma control. CONCLUSIONS: The variable humoral response to rhinovirus species in both groups, suggests a differential infectivity pattern between rhinovirus species. In healthy pre-schoolers, rhinovirus antibodies accumulate with colds. In asthma, rhinovirus A and rhinovirus C antibodies are much higher and further increase with disease severity and wheeze episodes. Higher antibody levels in asthma may be due to a compromised innate immune response, leading to increased exposure of the adaptive immunity to the virus. Importantly, there is no apparent protection with increasing levels of antibodies.

Published
2018

275. Regulatory Immune Mechanisms in Tolerance to Food Allergy

Author

Satitsuksanoa, Pattraporn, Jansen, Kirstin, Głobińska, Anna, van de Veen, Willem, Akdis, Mübeccel, Satitsuksanoa, Pattraporn, Jansen, Kirstin, Głobińska, Anna, van de Veen, Willem, and Akdis, Mübeccel

Abstract

Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.

Published
2018

278. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Cossarizza, Andrea, Chang, Hyun-Dong, Radbruch, Andreas, Akdis, Mübeccel, et al, Becher, Burkhard, Engelhardt, B, LeibundGut-Landmann, Salomé, Ludewig, B, Oxenius, Annette, University of Zurich, and Cossarizza, Andrea

Subjects
2403 Immunology, Immunology, 2723 Immunology and Allergy, 570 Life sciences, biology, Immunology and Allergy, 610 Medicine & health, 10263 Institute of Experimental Immunology, 10244 Institute of Virology
Published
2017

281. Handling of allergen immunotherapy in the COVID‐19 pandemic: An ARIA‐EAACI statement.

Author

Pfaar, Oliver, Klimek, Ludger, Jutel, Marek, Akdis, Cezmi, Bousquet, Jean, Akdis, Mübeccel, Bachert, Claus, Agache, Ioana, Ansotegui, Ignacio, Bedbrook, Anna, Bosnic‐Anticevich, Sinthia, Canonica, Giorgio W., Chivato, Tomas, Cruz, Alvaro A., Czarlewski, Wienia, Del Giacco, Stefano, Du, Hui, Fonseca, Joao A., Gao, Yadong, and Haahtela, Tari

Subjects
COVID-19 pandemic, ALLERGIC conjunctivitis, COVID-19, MERS coronavirus, ALLERGENS
Abstract

Handling of allergen immunotherapy in the COVID-19 pandemic: An ARIA-EAACI statement Keywords: allergy treatment; immunotherapy clinical; immunotherapy vaccines and mechanisms EN allergy treatment immunotherapy clinical immunotherapy vaccines and mechanisms 1546 1554 9 07/14/20 20200701 NES 200701 INTRODUCTION The current COVID-19 pandemic influences many areas of social life, medical treatments and the way allergy diagnosis and treatment is performed. This manuscript outlines the EAACI recommendations regarding AIT during the COVID-19 pandemic and aims at supporting allergists and all physicians performing AIT in their current daily practice with clear recommendations how to perform treatment during the pandemic and in SARS-CoV-2 infected patients. AIT can also be continued as usual in patients without clinical symptoms and signs of COVID-19 or other infections and without a history of exposure to SARS-CoV-2 or contact to COVID-19 confirmed individuals within the past 14 days. [Extracted from the article]

Published
2020
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282. Impact of high‐altitude therapy on type‐2 immune responses in asthma patients.

Author

Boonpiyathad, Tadech, Capova, Gertruda, Duchna, Hans‐Werner, Croxford, Andrew L., Farine, Herve, Dreher, Anita, Clozel, Martine, Schreiber, Juliane, Kubena, Petr, Lunjani, Nonhlanhla, Mirer, David, Rückert, Beate, Satitsuksanoa, Pattraporn, Tan, Ge, Groenen, Peter M. A., Bersuch, Eugen, Akdis, Mübeccel, Strasser, Daniel S., Renner, Ellen D., and Akdis, Cezmi A.

Subjects
ASTHMATICS, IMMUNE response, TH2 cells, INNATE lymphoid cells, T cells
Abstract

Background: Asthma patients present with distinct immunological profiles, with a predominance of type 2 endotype. The aim of this study was to investigate the impact of high‐altitude treatment on the clinical and immunological response in asthma. Methods: Twenty‐six hospitalized asthma patients (nine eosinophilic allergic; EA, nine noneosinophilic allergic; NEA and eight noneosinophilic nonallergic; NN) and nine healthy controls in high altitude for 21 days were enrolled in the study. We assessed eosinophils, T cells, Tregs, and innate lymphoid cells (ILC) from peripheral blood using flow cytometry. Results: The number of eosinophils (both resting and activated) and chemoattractant receptor homolog expressed on Th2 cells (CRTH2)‐expressing CD4+ and CD8+ T cells decreased significantly in EA patients after altitude treatment. The frequency of CRTH2+ Tregs as decreased significantly in all the asthma phenotypes as well as the frequency of ILC2 was significantly reduced in EA after altitude treatment. After 21 days of altitude therapy, CRTH2‐expressing ILC2, CD4+ and CD8+ T cells and Treg cells showed attenuated responses to exogenous PGD2. Furthermore, PGD2 signaling via CRTH2 was found to diminish the suppressive function of CRTH2+ Tregs which partially normalized during high‐altitude treatment. Improved asthma control was particularly evident in allergic asthma patients and correlated with decreased frequencies of CRTH2+ Treg cells in EA patients. Serum IL‐5 and IL‐13 decreased during climate treatment in asthma patients with high baseline levels. Conclusions: Asthma treatment in high altitude reduced the type 2 immune response, corrected the increased CRTH2 expression and its dysregulated functions. [ABSTRACT FROM AUTHOR]

Published
2020
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284. Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44

Author

Shan, Meimei, primary, Carrillo, Jorge, additional, Yeste, Ada, additional, Gutzeit, Cindy, additional, Segura-Garzón, Daniel, additional, Walland, A. Cooper, additional, Pybus, Marc, additional, Grasset, Emilie K., additional, Yeiser, John R., additional, Matthews, Dean B., additional, van de Veen, Willem, additional, Comerma, Laura, additional, He, Bing, additional, Boonpiyathad, Tadech, additional, Lee, Haekyung, additional, Blanco, Julià, additional, Osborne, Lisa C., additional, Siracusa, Mark C., additional, Akdis, Mübeccel, additional, Artis, David, additional, Mehandru, Saurabh, additional, Sampson, Hugh A., additional, Berin, M. Cecilia, additional, Chen, Kang, additional, and Cerutti, Andrea, additional

Published
2018
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285. Mechanisms of allergen-specific immunotherapy

Author

Głobińska, Anna, primary, Boonpiyathad, Tadech, additional, Satitsuksanoa, Pattraporn, additional, Kleuskens, Mirelle, additional, van de Veen, Willem, additional, Sokolowska, Milena, additional, and Akdis, Mübeccel, additional

Published
2018
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286. Human CD40 ligand–expressing type 3 innate lymphoid cells induce IL-10–producing immature transitional regulatory B cells

Author

Komlósi, Zsolt I., primary, Kovács, Nóra, additional, van de Veen, Willem, additional, Kirsch, Anna Isabella, additional, Fahrner, Heinz Benedikt, additional, Wawrzyniak, Marcin, additional, Rebane, Ana, additional, Stanic, Barbara, additional, Palomares, Oscar, additional, Rückert, Beate, additional, Menz, Günter, additional, Akdis, Mübeccel, additional, Losonczy, György, additional, and Akdis, Cezmi A., additional

Published
2018
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287. Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis

Author

Mikola, Emilia, primary, Elenius, Varpu, additional, Saarinen, Maria, additional, Palomares, Oscar, additional, Waris, Matti, additional, Turunen, Riitta, additional, Puhakka, Tuomo, additional, Ivaska, Lotta, additional, Rückert, Beate, additional, Aab, Alar, additional, Vahlberg, Tero, additional, Vuorinen, Tytti, additional, Allander, Tobias, additional, Camargo, Carlos A., additional, Akdis, Mübeccel, additional, Akdis, Cezmi A., additional, and Jartti, Tuomas, additional

Published
2018
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289. A Fluorescent Probe to Unravel Functional Features of Cannabinoid Receptor CB1 in Human Blood and Tonsil Immune System Cells

Author

Martín-Fontecha, Mar, primary, Angelina, Alba, additional, Rückert, Beate, additional, Rueda-Zubiaurre, Ainoa, additional, Martín-Cruz, Leticia, additional, van de Veen, Willem, additional, Akdis, Mübeccel, additional, Ortega-Gutiérrez, Silvia, additional, López-Rodríguez, María Luz, additional, Akdis, Cezmi A., additional, and Palomares, Oscar, additional

Published
2018
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290. Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis

Author

Frei, Remo, primary, Ferstl, Ruth, additional, Roduit, Caroline, additional, Ziegler, Mario, additional, Schiavi, Elisa, additional, Barcik, Weronika, additional, Rodriguez-Perez, Noelia, additional, Wirz, Oliver F., additional, Wawrzyniak, Marcin, additional, Pugin, Benoit, additional, Nehrbass, Dirk, additional, Jutel, Marek, additional, Smolinska, Sylwia, additional, Konieczna, Patrycja, additional, Bieli, Christian, additional, Loeliger, Susanne, additional, Waser, Marco, additional, Pershagen, Göran, additional, Riedler, Josef, additional, Depner, Martin, additional, Schaub, Bianca, additional, Genuneit, Jon, additional, Renz, Harald, additional, Pekkanen, Juha, additional, Karvonen, Anne M., additional, Dalphin, Jean-Charles, additional, van Hage, Marianne, additional, Doekes, Gert, additional, Akdis, Mübeccel, additional, Braun-Fahrländer, Charlotte, additional, Akdis, Cezmi A., additional, von Mutius, Erika, additional, O’Mahony, Liam, additional, Lauener, Roger P., additional, Alfvén, Tobias, additional, Alm, Johan, additional, Bergström, Anna, additional, Engstrand, Lars, additional, Rosenlund, Helen, additional, Hakansson, Niclas, additional, Lilja, Gunnar, additional, Nyberg, Frederik, additional, Swartz, Jackie, additional, Wickman, Magnus, additional, Wildhaber, Johannes, additional, Möller, Alex, additional, Brunekreef, Bert, additional, Boeve, Mirian, additional, Douwes, Jeroen, additional, Huber, Machteld, additional, Gertraud Weiss, Mirjam Matze, additional, Schreue, Mynda, additional, Michles, Karin B., additional, Sennhauser, Felix, additional, Scheynius, Annika, additional, Hirvonen, Maija-Riitta, additional, Remes, Sami, additional, Roponen, Marjut, additional, Tiittanen, Pekka, additional, Dalphin, Marie-Laure, additional, Gisela Buchele, Vincent Kaulek, additional, Ege, Markus, additional, Kabesch, Michael, additional, Pfefferle, Petra, additional, Loss, Georg, additional, and Hyvärinen, Anne, additional

Published
2018
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291. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients

Author

Sugita, Kazunari, primary, Steer, Catherine A., additional, Martinez-Gonzalez, Itziar, additional, Altunbulakli, Can, additional, Morita, Hideaki, additional, Castro-Giner, Francesc, additional, Kubo, Terufumi, additional, Wawrzyniak, Paulina, additional, Rückert, Beate, additional, Sudo, Katsuko, additional, Nakae, Susumu, additional, Matsumoto, Kenji, additional, O'Mahony, Liam, additional, Akdis, Mübeccel, additional, Takei, Fumio, additional, and Akdis, Cezmi A., additional

Published
2018
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293. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Translationele immunologie, Infection & Immunity, Cossarizza, Andrea, Chang, Hyun-Dong, Radbruch, Andreas, Akdis, Mübeccel, Andrä, Immanuel, Annunziato, Francesco, Bacher, Petra, Barnaba, Vincenzo, Battistini, Luca, Bauer, Wolfgang M, Baumgart, Sabine, Becher, Burkhard, Beisker, Wolfgang, Berek, Claudia, Blanco, Alfonso, Borsellino, Giovanna, Boulais, Philip E, Brinkman, Ryan R, Büscher, Martin, Busch, Dirk H., Bushnell, Timothy P, Cao, Xuetao, Cavani, Andrea, Chattopadhyay, Pratip K, Cheng, Qingyu, Chow, Sue, Clerici, Mario, Cooke, Anne, Cosma, Antonio, Cosmi, Lorenzo, Cumano, Ana, Dang, Van Duc, Davies, Derek, De Biasi, Sara, Del Zotto, Genny, Della Bella, Silvia, Dellabona, Paolo, Deniz, Günnur, Dessing, Mark, Diefenbach, Andreas, Santo, James P.Di, Dieli, Francesco, Dolf, Andreas, Donnenberg, Vera S, Dörner, Thomas, Ehrhardt, Götz R A, Endl, Elmar, Engel, Pablo, Engelhardt, Britta, Esser, Charlotte, Everts, Bart, Dreher, Anita, Falk, Christine S, Fehniger, Todd A, Filby, Andrew, Fillatreau, Simon, Follo, Marie, Förster, Irmgard, Foster, John, Foulds, Gemma A, Frenette, Paul S, Galbraith, David, Garbi, Natalio, García-Godoy, Maria Dolores, Geginat, Jens, Ghoreschi, Kamran, Gibellini, Lara, Goettlinger, Christoph, Goodyear, Carl S, Gori, Andrea, Grogan, Jane, Gross, Mor, Grützkau, Andreas, Grummitt, Daryl, Hahn, Jonas, Hammer, Quirin, Hauser, Anja E, Haviland, David L, Hedley, David, Herrera, Guadalupe, Herrmann, Martin, Hiepe, Falk, Holland, Tristan, Hombrink, Pleun, Houston, Jessica P, Hoyer, Bimba F, Huang, Bo, Hunter, Christopher A, Iannone, Anna G., Jäck, Hans-Martin, Jávega, Beatriz, Jonjic, Stipan, Juelke, Kerstin, Jung, Steffen, Kaiser, Toralf, Kalina, Tomas, Keller, Baerbel, Khan, Srijit, Kienhöfer, Deborah, Kroneis, Thomas, Kunkel, Désirée, Kurts, Christian, Kvistborg, Pia, Lannigan, Joanne, Lantz, Olivier, Larbi, Anis, LeibundGut-Landmann, Salome, Leipold, Michael D, Levings, Megan K, Litwin, Virginia, Liu, Yanling, Lohoff, Michael, Lombardi, Giovanna, Lopez, Lilly, Lovett-Racke, Amy, Lubberts, Erik, Ludewig, Burkhard, Lugli, Enrico, Maecker, Holden T, Martrus, Glòria, Matarese, Giuseppe, Maueröder, Christian, McGrath, Mairi, McInnes, Iain B., Mei, Henrik E, Melchers, Fritz, Melzer, Susanne, Mielenz, Dirk, Mills, Kingston, Mirrer, David, Mjösberg, Jenny, Moore, Jonni, Moran, Barry, Moretta, Alessandro, Moretta, Lorenzo, Mosmann, Tim R, Müller, Susann, Müller, Werner, Münz, Christian, Multhoff, Gabriele, Munoz, Luis Enrique, Murphy, Kenneth M, Nakayama, Toshinori, Nasi, Milena, Neudörfl, Christine, Nolan, John J., Nourshargh, Sussan, O'Connor, José-Enrique, Ouyang, Wenjun, Oxenius, Annette, Palankar, Raghav, Panse, Isabel, Peterson, Pärt, Peth, Christian, Petriz, Jordi, Philips, Daisy, Pickl, Winfried, Piconese, Silvia, Pinti, Marcello, Pockley, A Graham, Podolska, Malgorzata Justyna, Pucillo, Carlo, Quataert, Sally A, Radstake, Timothy R D J, Rajwa, Bartek, Rebhahn, Jonathan A, Recktenwald, Diether, Remmerswaal, Ester B M, Rezvani, Katy, Rico, Laura G, Robinson, J Paul, Romagnani, Chiara, Rubartelli, Anna, Ruckert, Beate, Ruland, Jürgen, Sakaguchi, Shimon, Sala-de-Oyanguren, Francisco, Samstag, Yvonne, Sanderson, Sharon, Sawitzki, Birgit, Scheffold, Alexander, Schiemann, Matthias, Schildberg, Frank, Schimisky, Esther, Schmid, Stephan A, Schmitt, Steffen, Schober, Kilian, Schüler, Thomas, Schulz, Axel Ronald, Schumacher, Ton N., Scotta, Cristiano, Shankey, T Vincent, Shemer, Anat, Simon, Anna-Katharina, Spidlen, Josef, Stall, Alan M, Stark, Regina, Stehle, Christina, Stein, Merle, Steinmetz, Tobit, Stockinger, Hannes, Takahama, Yousuke, Tarnok, Attila, Tian, ZhiGang, Toldi, Gergely, Tornack, Julia, Traggiai, Elisabetta, Trotter, Joe, Ulrich, Henning, van der Braber, Marlous, van Lier, René A W, Veldhoen, Marc, Vento-Asturias, Salvador, Vieira, Paulo, Voehringer, David, Volk, Hans-Dieter, von Volkmann, Konrad, Waisman, Ari, Walker, Rachael, Ward, Michael D, Warnatz, Klaus, Warth, Sarah, Watson, James V, Watzl, Carsten, Wegener, Leonie, Wiedemann, Annika, Wienands, Jürgen, Willimsky, Gerald, Wing, James, Wurst, Peter, Yu, Liping, Yue, Alice, Zhang, Qianjun, Zhao, Yi, Ziegler, Susanne, Zimmermann, Jakob, Translationele immunologie, Infection & Immunity, Cossarizza, Andrea, Chang, Hyun-Dong, Radbruch, Andreas, Akdis, Mübeccel, Andrä, Immanuel, Annunziato, Francesco, Bacher, Petra, Barnaba, Vincenzo, Battistini, Luca, Bauer, Wolfgang M, Baumgart, Sabine, Becher, Burkhard, Beisker, Wolfgang, Berek, Claudia, Blanco, Alfonso, Borsellino, Giovanna, Boulais, Philip E, Brinkman, Ryan R, Büscher, Martin, Busch, Dirk H., Bushnell, Timothy P, Cao, Xuetao, Cavani, Andrea, Chattopadhyay, Pratip K, Cheng, Qingyu, Chow, Sue, Clerici, Mario, Cooke, Anne, Cosma, Antonio, Cosmi, Lorenzo, Cumano, Ana, Dang, Van Duc, Davies, Derek, De Biasi, Sara, Del Zotto, Genny, Della Bella, Silvia, Dellabona, Paolo, Deniz, Günnur, Dessing, Mark, Diefenbach, Andreas, Santo, James P.Di, Dieli, Francesco, Dolf, Andreas, Donnenberg, Vera S, Dörner, Thomas, Ehrhardt, Götz R A, Endl, Elmar, Engel, Pablo, Engelhardt, Britta, Esser, Charlotte, Everts, Bart, Dreher, Anita, Falk, Christine S, Fehniger, Todd A, Filby, Andrew, Fillatreau, Simon, Follo, Marie, Förster, Irmgard, Foster, John, Foulds, Gemma A, Frenette, Paul S, Galbraith, David, Garbi, Natalio, García-Godoy, Maria Dolores, Geginat, Jens, Ghoreschi, Kamran, Gibellini, Lara, Goettlinger, Christoph, Goodyear, Carl S, Gori, Andrea, Grogan, Jane, Gross, Mor, Grützkau, Andreas, Grummitt, Daryl, Hahn, Jonas, Hammer, Quirin, Hauser, Anja E, Haviland, David L, Hedley, David, Herrera, Guadalupe, Herrmann, Martin, Hiepe, Falk, Holland, Tristan, Hombrink, Pleun, Houston, Jessica P, Hoyer, Bimba F, Huang, Bo, Hunter, Christopher A, Iannone, Anna G., Jäck, Hans-Martin, Jávega, Beatriz, Jonjic, Stipan, Juelke, Kerstin, Jung, Steffen, Kaiser, Toralf, Kalina, Tomas, Keller, Baerbel, Khan, Srijit, Kienhöfer, Deborah, Kroneis, Thomas, Kunkel, Désirée, Kurts, Christian, Kvistborg, Pia, Lannigan, Joanne, Lantz, Olivier, Larbi, Anis, LeibundGut-Landmann, Salome, Leipold, Michael D, Levings, Megan K, Litwin, Virginia, Liu, Yanling, Lohoff, Michael, Lombardi, Giovanna, Lopez, Lilly, Lovett-Racke, Amy, Lubberts, Erik, Ludewig, Burkhard, Lugli, Enrico, Maecker, Holden T, Martrus, Glòria, Matarese, Giuseppe, Maueröder, Christian, McGrath, Mairi, McInnes, Iain B., Mei, Henrik E, Melchers, Fritz, Melzer, Susanne, Mielenz, Dirk, Mills, Kingston, Mirrer, David, Mjösberg, Jenny, Moore, Jonni, Moran, Barry, Moretta, Alessandro, Moretta, Lorenzo, Mosmann, Tim R, Müller, Susann, Müller, Werner, Münz, Christian, Multhoff, Gabriele, Munoz, Luis Enrique, Murphy, Kenneth M, Nakayama, Toshinori, Nasi, Milena, Neudörfl, Christine, Nolan, John J., Nourshargh, Sussan, O'Connor, José-Enrique, Ouyang, Wenjun, Oxenius, Annette, Palankar, Raghav, Panse, Isabel, Peterson, Pärt, Peth, Christian, Petriz, Jordi, Philips, Daisy, Pickl, Winfried, Piconese, Silvia, Pinti, Marcello, Pockley, A Graham, Podolska, Malgorzata Justyna, Pucillo, Carlo, Quataert, Sally A, Radstake, Timothy R D J, Rajwa, Bartek, Rebhahn, Jonathan A, Recktenwald, Diether, Remmerswaal, Ester B M, Rezvani, Katy, Rico, Laura G, Robinson, J Paul, Romagnani, Chiara, Rubartelli, Anna, Ruckert, Beate, Ruland, Jürgen, Sakaguchi, Shimon, Sala-de-Oyanguren, Francisco, Samstag, Yvonne, Sanderson, Sharon, Sawitzki, Birgit, Scheffold, Alexander, Schiemann, Matthias, Schildberg, Frank, Schimisky, Esther, Schmid, Stephan A, Schmitt, Steffen, Schober, Kilian, Schüler, Thomas, Schulz, Axel Ronald, Schumacher, Ton N., Scotta, Cristiano, Shankey, T Vincent, Shemer, Anat, Simon, Anna-Katharina, Spidlen, Josef, Stall, Alan M, Stark, Regina, Stehle, Christina, Stein, Merle, Steinmetz, Tobit, Stockinger, Hannes, Takahama, Yousuke, Tarnok, Attila, Tian, ZhiGang, Toldi, Gergely, Tornack, Julia, Traggiai, Elisabetta, Trotter, Joe, Ulrich, Henning, van der Braber, Marlous, van Lier, René A W, Veldhoen, Marc, Vento-Asturias, Salvador, Vieira, Paulo, Voehringer, David, Volk, Hans-Dieter, von Volkmann, Konrad, Waisman, Ari, Walker, Rachael, Ward, Michael D, Warnatz, Klaus, Warth, Sarah, Watson, James V, Watzl, Carsten, Wegener, Leonie, Wiedemann, Annika, Wienands, Jürgen, Willimsky, Gerald, Wing, James, Wurst, Peter, Yu, Liping, Yue, Alice, Zhang, Qianjun, Zhao, Yi, Ziegler, Susanne, and Zimmermann, Jakob

Published
2017

294. Role of Regulatory Cells in Oral Tolerance

Author

Wawrzyniak, Marcin, O'Mahony, Liam, Akdis, Mübeccel, Wawrzyniak, Marcin, O'Mahony, Liam, and Akdis, Mübeccel

Abstract

The immune system is continuously exposed to great amounts of different antigens from both food and intestinal microbes. Immune tolerance to these antigens is very important for intestinal and systemic immune homeostasis. Oral tolerance is a specific type of peripheral tolerance induced by exposure to antigen via the oral route. Investigations on the role of intestinal immune system in preventing hypersensitivity reactions to innocuous dietary and microbial antigens have been intensively performed during the last 2 decades. In this review article, we discuss how food allergens are recognized by the intestinal immune system and draw attention to the role of regulatory T (Treg) and B (Breg) cells in the establishment of oral tolerance and tolerogenic features of intestinal dendritic cells. We also emphasize the potential role of tonsils in oral tolerance induction because of their anatomical location, cellular composition, and possible usage to develop novel ways of specific immunotherapy for the treatment of allergic diseases.

Published
2017

295. The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response

Author

Elenius, Varpu, Palomares, Oscar, Waris, Matti, Turunen, Riitta, Puhakka, Tuomo, Rückert, Beate, Vuorinen, Tytti, Allander, Tobias, Vahlberg, Tero, Akdis, Mübeccel, Camargo, Carlos A, Akdis, Cezmi A, Jartti, Tuomas, Elenius, Varpu, Palomares, Oscar, Waris, Matti, Turunen, Riitta, Puhakka, Tuomo, Rückert, Beate, Vuorinen, Tytti, Allander, Tobias, Vahlberg, Tero, Akdis, Mübeccel, Camargo, Carlos A, Akdis, Cezmi A, and Jartti, Tuomas

Published
2017

297. List of Contributors

Author

Aceves, Seema S., Adcock, Ian M., Akdis, Cezmi A., Akdis, Mübeccel, Akuthota, Praveen, Allnutt, Katherine J., Apter, Andrea J., Bacharier, Leonard B., Bachert, Claus, Baines, Katherine J., Ballow, Mark, Bankova, Lora, Barnes, Peter J., Barney, Neal P., Baroody, Fuad M., Barrett, Nora, Baumert, Joseph L., Bender, Bruce G., Berin, M. Cecilia, Myers, Jocelyn M. Biagini, Blake, Kathryn V., Bochner, Bruce S., Boguniewicz, Mark, Borish, Larry, Boulet, Louis-Philippe, Bousquet, Jean, Boyce, Joshua A., Bradding, Peter, Brannan, John D., Bridgewater, Jennifer L., Brightling, Christopher E., Broide, David H., Buckley, Rebecca H., Bunyavanich, Supinda, Burks, A. Wesley, Bush, Robert K., Busse, William W., Camargo, Carlos A., Jr., Camiolo, Matthew, Canning, Brendan J., Casale, Thomas B., Castro, Mario, Chambers, Christina, Chinen, Javier, Chinn, Ivan, Chiriac, Anca Mirela, Christiansen, Sandra C., Chung, K. Fan, Cockcroft, Donald W., Cohain, Ariella T., Cohn, Lauren, Commins, Scott P., Corren, Jonathan, Cousins, David J., Custovic, Adnan, Davies, Janet M., Demoly, Pascal, Diepgen, Thomas L., Doherty, Taylor A., Dolovich, Myrna B., Eng, B, Eng, P, Douglass, Jo A., Dreskin, Stephen C., Durrani, Sandy R., Dykewicz, Mark S., Eccles, Ronald, Edwards, Alan M., Eiwegger, Thomas, Engel, Pablo, Engler, Renata J.M., Fajt, Merritt L., Fain, Sean B., Fontana, Joseph R., Frank, Michael M., Frew, Anthony J., Fricker, Michael, Garn, Holger, Gauthier, Marc, George, Maureen, Gevaert, Philippe, Gibson, Peter G., Godbout, Krystelle, Golden, David B.K., Grumach, Anete S., Guilbert, Theresa W., Gunawardana, Natasha, Gupta, Sudhir, Hallstrand, Teal S., Hamilton, Robert G., Hammad, Hamida, Hernandez, Michelle L., Khurana Hershey, Gurjit K., Hester, C. Garren, Hew, Mark, Hirota, Jeremy, Holgate, Stephen T., Holloway, John W., Irvin, Charles G., Irwin, Richard S., Jackson, Daniel J., Janssen, William J., Jelinek, Diane F., Jones, Stacie M., Kaminsky, David A., Kelly, Margaret M., Kelso, John M., Khoury, Paneez, Kita, Hirohito, Klion, Amy D., Knight, Darryl, Kowalski, Marek L., Koziol-White, Cynthia J., Lack, Gideon, Laidlaw, Tanya M., Lambrecht, Bart N., Langford, Carol A., Laube, Beth L., LeBlanc, Stephen B., Leiding, Jennifer W., Lehman, Heather K., Lemanske, Robert F., Jr., Lemière, Catherine, Leung, Donald Y.M., Li, James T., Li, Xiu-Min, Lloyd, Clare, Luster, Andrew D., Macy, Eric, Madison, J. Mark, Mangold, Aaron R., Marsh, Rebecca A., Marshall, Gailen D., Jr., Matsui, Elizabeth, Mersha, Tesfaye B., Metcalfe, Dean D., Mikhak, Zamaneh, Mills, E.N. Clare, Nelson, Harold S., Nixon, Rosemary L., Nowak-Węgrzyn, Anna, O'Byrne, Paul M., Oettgen, Hans C., O'Hehir, Robyn E., Orange, Jordan S., Ownby, Dennis R., Page, Clive P., Panettieri, Reynold A., Jr., Park, Hae-Sim, Paul, Mary E., Peden, David B., Peebles, R. Stokes, Jr., Peters, Stephen P., Peters-Golden, Marc, Phillips, Elizabeth J., Pittelkow, Mark R., Platts-Mills, Thomas A.E., Prescott, Susan L., Rabin, Ronald L., Raissy, Hengameh H., Ray, Anuradha, Ray, Samriddha, Renz, Harald, Robinson, Clive, Rosenberg, Chen E., Rothenberg, Marc E., Rowe, Brian H., Saglani, Sejal, Sahin, Ozlem, Saini, Sarbjit S., Saito, Hirohisa, Sampson, Hugh A., Satia, Imran, Sayers, Ian, Scadding, Guy W., Schadt, Eric E., Schatz, Michael, Schauberger, Eric, Schroeder, John T., Seroogy, Christine M., Shearer, William T., Shelhamer, James H., Siberry, George K., Sicherer, Scott H., Simons, F. Estelle R., Simpson, Jodie L., Slater, Jay E., AO, Peter D. Sly, Smith, Helen E., Smith, Philip H., Sokol, Caroline L., Solensky, Roland, Sriramarao, P., Srivastava, Kamal, Steinke, John W., Stewart, Geoffrey A., Stitt, Jenny M., Stokes, Jeffrey R., Sullivan, Kathleen E., Tay, Tunn Ren, Taylor, Steve L., Thompson, Bruce, Togias, Alkis, Tovey, Euan, Tuano, Karen S., Undem, Bradley J., Vandenplas, Olivier, van Zelm, Menno C., Viswanathan, Ravi K., Weber, Richard W., Weller, Peter F., Wenzel, Sally E., Whitsett, Jeffrey A., Wood, Robert A., Yel, Leman, Zeiger, Robert S., Zhang, Nan, and Zuraw, Bruce L.

Published
2020
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299. Regulation of bronchial epithelial barrier integrity by type 2 cytokines and histone deacetylases in asthma

Author

Wawrzyniak, Paulina, Wawrzyniak, Marcin, Wanke, Kerstin, Sokolowska, Milena, Bendelja, Kreso, Rückert, Beate, Globinska, Anna, Jakiela, Bogdan, Kast, Jeannette I, Idzko, Marco, Akdis, Mübeccel, Sanak, Marek, and Akdis, Cezmi A

Subjects
asthma, histone deacetylases, bronchial epithelial barrier
Abstract

Tight junctions (TJs) form a barrier on the apical side of neighboring epithelial cells in the bronchial mucosa. Changes in their integrity might play a role in asthma pathogenesis by enabling the paracellular influx of allergens, toxins, and microbes to the submucosal tissue. The regulation of bronchial epithelial TJs by TH2 cells and their cytokines and their involvement in epigenetic regulation of barrier function were investigated. The expression, regulation, and function of TJs were determined in air-liquid interface (ALI) cultures of control and asthmatic primary human bronchial epithelial cells (HBECs) by means of analysis of transepithelial electrical resistance, paracellular flux, mRNA expression, Western blotting, and immunofluorescence staining. HBECs from asthmatic patients showed a significantly low TJ integrity in ALI cultures compared with HBECs from healthy subjects. TH2 cell numbers and levels of their cytokines, IL-4 and IL-13, decreased barrier integrity in ALI cultures of HBECs from control subjects but not in HBECs from asthmatic patients. They induced a physical separation of the TJs of adjacent cells in immunofluorescence staining of the TJ molecules occludin and zonula occludens-1. We observed that expression of histone deacetylases (HDACs) 1 and 9, and Silent information regulator genes (sirtuins [SIRTs]) 6 and 7 were significantly high in HBECs from asthmatic patients. IL-4 and IL-13 significantly increased the expression of HDACs and SIRTs. The role of HDAC activation on epithelial barrier leakiness was confirmed by HDAC inhibition, which improved barrier integrity through increased synthesis of TJ molecules in epithelium from asthmatic patients to the level seen in HBECs from control subjects. Our data demonstrate that barrier leakiness in asthmatic patients is induced by TH2 cells, IL-4, and IL-13 and HDAC activity. The inhibition of endogenous HDAC activity reconstitutes defective barrier by increasing TJ expression.

Published
2016

300. 気管支上皮のバリア維持におけるCpG-DNAの役割

Author

Kubo, Terufumi, Wawrzyniak, Paulina, Morita, Hideaki, Sugita, Kazunari, Wanke, Kerstin, Kast, Jeannette I, Altunubulakli, Can, Rückert, Beate, Akdis, Mübeccel, Akdis, Cezmi A, and University of Zurich

Subjects
10183 Swiss Institute of Allergy and Asthma Research, 610 Medicine & health
Published
2016

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