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J Allergy Clin Immunol. 2018 Jan;141(1):382-390.e7. doi: 10.1016/j.jaci.2017.04.051. Epub 2017 Jun 17.

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

Author information

1
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. Electronic address: remo.frei@siaf.uzh.ch.
2
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
3
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital, University of Zurich, Zurich, Switzerland.
4
AO Research Institute Davos, Davos, Switzerland.
5
Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland; "ALL-MED" Medical Research Institute, Wroclaw, Poland.
6
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
7
Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
8
Children's Hospital Schwarzach, Schwarzach, Austria.
9
Dr von Hauner Children's Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
10
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
11
Institute for Laboratory Medicine, Pathobiochemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
12
Department of Environment Health, National Institute for Health and Welfare, Kuopio, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
13
Department of Environment Health, National Institute for Health and Welfare, Kuopio, Finland.
14
Department of Respiratory Disease, UMR/CNRS 6249 Chrono-environment, University Hospital of Besançon, Besançon, France.
15
Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
16
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
17
Dr von Hauner Children's Hospital, Ludwig-Maximilians-Universität, Munich, Germany; CPC_M, Member of the German Center for Lung Research, Munich, Germany.
18
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital of Eastern Switzerland, St Gallen, Switzerland. Electronic address: roger.lauener@kispisg.ch.

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.

KEYWORDS:

Farmers' children; N-glycolylneuraminic acid; airway inflammation; anti-inflammatory; colitis; nonmicrobial

PMID:
28629745
DOI:
10.1016/j.jaci.2017.04.051
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