M-V Martikainen1, H Kääriö1, A Karvonen2, P C Schröder3,4, H Renz5, V Kaulek6, J-C Dalphin6, E von Mutius3,4, B Schaub3,4, J Pekkanen7, M-R Hirvonen1,2, M Roponen1. 1. Department of Environmental Science, University of Eastern Finland, Kuopio, Finland. 2. Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland. 3. Department of Allergy and Pulmonary, University Children's Hospital, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany. 4. Member of the German Center for Lung Research (DZL), Munich, Germany. 5. Institute of Laboratory Medicine, Pathobiochemistry and Molecular Diagnostics, Philipps University, Marburg, Germany. 6. Department of Respiratory Disease, UMR/CNRS 6249 Chrono-Environment, University Hospital of Besançon, Besançon, France. 7. Department of Public Health, University of Helsinki, Helsinki, Finland.
Abstract
BACKGROUND: Early life farm exposures have been shown to decrease the risk of allergic diseases. Dendritic cells (DCs) may mediate asthma-protective effect of farm exposures as they play an important role in the development of immunity and tolerance. Our aim was to investigate whether the numbers and phenotypes of circulating DCs at age 6 are associated with farming, asthma, and atopy in a selected sample of French and Finnish children from the PASTURE study. METHODS: We studied 82 farm and 86 nonfarm children with and without asthma. Using flow cytometry, BDCA1+ CD11c+ myeloid DC1s (mDC1), BDCA3+(high) mDC2s and BDCA2+ plasmacytoid DCs (pDCs) were identified and expressions of CD86, immunoglobulin-like transcript 3 (ILT3) and ILT4 were analyzed. Questionnaires were used to assess prenatal and lifetime patterns of farm exposures and to define asthma. Atopic sensitization was defined by specific IgE measurements. RESULTS: The percentage of mDC2 cells was lower in farm children (0.033 ± 0.001) than in nonfarm children (0.042 ± 0.001; P = 0.008). Similar associations were found between mDC2 percentage and prenatal (P = 0.02) and lifetime exposure to farm milk (P = 0.03) and stables (P = 0.003), but these associations were not independent from farming. Asthma was positively associated with ILT4 + mDCs (P = 0.04) and negatively with CD86 + pDCs (P = 0.048) but only in nonfarm children. CONCLUSIONS: Inverse association between farm exposure and mDC2 percentage suggest that this DC subset may play a role in farm-related immunoregulation.
BACKGROUND: Early life farm exposures have been shown to decrease the risk of allergic diseases. Dendritic cells (DCs) may mediate asthma-protective effect of farm exposures as they play an important role in the development of immunity and tolerance. Our aim was to investigate whether the numbers and phenotypes of circulating DCs at age 6 are associated with farming, asthma, and atopy in a selected sample of French and Finnish children from the PASTURE study. METHODS: We studied 82 farm and 86 nonfarm children with and without asthma. Using flow cytometry, BDCA1+ CD11c+ myeloid DC1s (mDC1), BDCA3+(high) mDC2s and BDCA2+ plasmacytoid DCs (pDCs) were identified and expressions of CD86, immunoglobulin-like transcript 3 (ILT3) and ILT4 were analyzed. Questionnaires were used to assess prenatal and lifetime patterns of farm exposures and to define asthma. Atopic sensitization was defined by specific IgE measurements. RESULTS: The percentage of mDC2 cells was lower in farm children (0.033 ± 0.001) than in nonfarm children (0.042 ± 0.001; P = 0.008). Similar associations were found between mDC2 percentage and prenatal (P = 0.02) and lifetime exposure to farm milk (P = 0.03) and stables (P = 0.003), but these associations were not independent from farming. Asthma was positively associated with ILT4 + mDCs (P = 0.04) and negatively with CD86 + pDCs (P = 0.048) but only in nonfarm children. CONCLUSIONS: Inverse association between farm exposure and mDC2 percentage suggest that this DC subset may play a role in farm-related immunoregulation.
Authors: Erika von Mutius; Juha Pekkanen; Pirkka V Kirjavainen; Anne M Karvonen; Rachel I Adams; Martin Täubel; Marjut Roponen; Pauli Tuoresmäki; Georg Loss; Balamuralikrishna Jayaprakash; Martin Depner; Markus Johannes Ege; Harald Renz; Petra Ina Pfefferle; Bianca Schaub; Roger Lauener; Anne Hyvärinen; Rob Knight; Dick J J Heederik Journal: Nat Med Date: 2019-06-17 Impact factor: 53.440