1. Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis
- Author
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Remo Frei, Ruth Ferstl, Caroline Roduit, Mario Ziegler, Elisa Schiavi, Weronika Barcik, Noelia Rodriguez-Perez, Oliver F. Wirz, Marcin Wawrzyniak, Benoit Pugin, Dirk Nehrbass, Marek Jutel, Sylwia Smolinska, Patrycja Konieczna, Christian Bieli, Susanne Loeliger, Marco Waser, Göran Pershagen, Josef Riedler, Martin Depner, Bianca Schaub, Jon Genuneit, Harald Renz, Juha Pekkanen, Anne M. Karvonen, Jean-Charles Dalphin, Marianne van Hage, Gert Doekes, Mübeccel Akdis, Charlotte Braun-Fahrländer, Cezmi A. Akdis, Erika von Mutius, Liam O’Mahony, Roger P. Lauener, Tobias Alfvén, Johan Alm, Anna Bergström, Lars Engstrand, Helen Rosenlund, Niclas Hakansson, Gunnar Lilja, Frederik Nyberg, Jackie Swartz, Magnus Wickman, Johannes Wildhaber, Alex Möller, Bert Brunekreef, Mirian Boeve, Jeroen Douwes, Machteld Huber, Mirjam Matze Gertraud Weiss, Mynda Schreue, Karin B. Michles, Felix Sennhauser, Annika Scheynius, Maija-Riitta Hirvonen, Sami Remes, Marjut Roponen, Pekka Tiittanen, Marie-Laure Dalphin, Vincent Kaulek Gisela Buchele, Markus Ege, Michael Kabesch, Petra Pfefferle, Georg Loss, Anne Hyvärinen, Ympäristö- ja biotieteiden laitos / Toiminta, School of Medicine / Public Health, dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), Department of Public Health, Clinicum, University of Helsinki, and University of Zurich
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HAY-FEVER ,0301 basic medicine ,Allergy ,colitis ,Respiratory Tract Diseases ,airway inflammation ,Severity of Illness Index ,Inflammatory bowel disease ,0302 clinical medicine ,ALLERGIC DISEASES ,10183 Swiss Institute of Allergy and Asthma Research ,T-Lymphocyte Subsets ,Immunology and Allergy ,Lymphocytes ,Child ,Sensitization ,anti-inflammatory ,Mice, Knockout ,RISK ,Farmers ,farmer's children ,Age Factors ,FOXP3 ,3142 Public health care science, environmental and occupational health ,3. Good health ,ATOPIC SENSITIZATION ,medicine.anatomical_structure ,Child, Preschool ,Population Surveillance ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,Hay fever ,medicine.symptom ,Farmers' children ,N-glycolylneuraminic acid ,Immunology ,610 Medicine & health ,EARLY-LIFE ,03 medical and health sciences ,Wheeze ,medicine ,Animals ,Humans ,Colitis ,Asthma ,Inflammation ,2403 Immunology ,NONHUMAN SIALIC-ACID ,business.industry ,Infant ,nonmicrobial ,Environmental Exposure ,SCHOOL-AGE-CHILDREN ,Allergens ,Immunoglobulin E ,medicine.disease ,Disease Models, Animal ,MICE ,Cross-Sectional Studies ,030104 developmental biology ,Immunoglobulin G ,3121 General medicine, internal medicine and other clinical medicine ,INNATE IMMUNITY ,ASTHMA ,Neuraminic Acids ,business ,Biomarkers - Abstract
Background Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. Objective We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. Methods Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. Results In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. Conclusions In addition to microbial exposure, increased exposure to non–microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment., published version, peerReviewed
- Published
- 2018