2.50
Hdl Handle:
http://hdl.handle.net/10033/71118
Title:
Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells.
Authors:
Schaub, Bianca; Liu, Jing; Höppler, Sabine; Schleich, Isolde; Huehn, Jochen; Olek, Sven; Wieczorek, Georg; Illi, Sabina; von Mutius, Erika
Abstract:
BACKGROUND: Cross-sectional studies suggest that maternal exposure to farming decreases the risk of allergic diseases in offspring. The potential underlying immunologic mechanisms are not understood. OBJECTIVE: We sought to assess whether maternal farm exposure activates regulatory T (Treg) cells in cord blood, exerting T(H)2-suppressive effects after microbial stimulation. METHODS: Eighty-four pregnant mothers were recruited before delivery. Detailed questionnaires (60 nonfarming and 22 farming mothers with 2 exclusions) assessed the farming exposures. Cord blood was stimulated with the microbial stimulus peptidoglycan (Ppg), the mitogen PHA, house dust mite extracts (Der p 1), and combinations. Treg cells (CD4+CD25(high) cells; intracellular forkhead/winged-helix family transcriptional repressor p3 [FOXP3] expression, FOXP3 levels, lymphocyte activation gene 3 mRNA expression, functional studies, and DNA methylation of the FOXP3 locus), proliferation, and T(H)2/T(H)1/T(H)17 cytokines were examined. RESULTS: Cord blood Treg cell counts (both unstimulated and PHA stimulated) were increased with maternal farming exposures and associated with higher FOXP3 (Der p 1 + Ppg stimulation) and trendwise higher lymphocyte activation gene 3 (Ppg) expression. Furthermore, Treg cell function was more efficient with farming exposure (effector cell suppression, P = .004). In parallel, T(H)2 cytokine (IL-5) levels were decreased and associated with decreased lymphoproliferation and increased IL-6 levels (Ppg stimulation, Der p 1 + Ppg stimulation, or both; P < .05). Maternal exposure to increasing numbers of farm animals and stables was discovered to exert distinct effects on Treg cells, T(H)1/T(H)2 cells, or both. Additionally, FOXP3 demethylation in offspring of mothers with farm milk exposure was increased (P = .02). CONCLUSIONS: Farm exposures during pregnancy increase the number and function of cord blood Treg cells associated with lower T(H)2 cytokine secretion and lymphocyte proliferation on innate exposure. One fascinating speculation is that maternal farm exposure might reflect a natural model of immunotherapy, potentially including a selection of innate stimuli in addition to allergen, shaping a child's immune system at an early stage.
Affiliation:
Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany. Bianca.Schaub@med.uni-muenchen.de
Citation:
Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. 2009, 123 (4):774-82.e5 J. Allergy Clin. Immunol.
Journal:
The Journal of allergy and clinical immunology
Issue Date:
Apr-2009
URI:
http://hdl.handle.net/10033/71118
DOI:
10.1016/j.jaci.2009.01.056
PubMed ID:
19348917
Type:
Article
Language:
en
ISSN:
1097-6825
Appears in Collections:
Publications of Dept. Experimental Immunology (EI)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchaub, Bianca-
dc.contributor.authorLiu, Jing-
dc.contributor.authorHöppler, Sabine-
dc.contributor.authorSchleich, Isolde-
dc.contributor.authorHuehn, Jochen-
dc.contributor.authorOlek, Sven-
dc.contributor.authorWieczorek, Georg-
dc.contributor.authorIlli, Sabina-
dc.contributor.authorvon Mutius, Erika-
dc.date.accessioned2009-06-22T13:20:17Z-
dc.date.available2009-06-22T13:20:17Z-
dc.date.issued2009-04-
dc.identifier.citationMaternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. 2009, 123 (4):774-82.e5 J. Allergy Clin. Immunol.en
dc.identifier.issn1097-6825-
dc.identifier.pmid19348917-
dc.identifier.doi10.1016/j.jaci.2009.01.056-
dc.identifier.urihttp://hdl.handle.net/10033/71118-
dc.description.abstractBACKGROUND: Cross-sectional studies suggest that maternal exposure to farming decreases the risk of allergic diseases in offspring. The potential underlying immunologic mechanisms are not understood. OBJECTIVE: We sought to assess whether maternal farm exposure activates regulatory T (Treg) cells in cord blood, exerting T(H)2-suppressive effects after microbial stimulation. METHODS: Eighty-four pregnant mothers were recruited before delivery. Detailed questionnaires (60 nonfarming and 22 farming mothers with 2 exclusions) assessed the farming exposures. Cord blood was stimulated with the microbial stimulus peptidoglycan (Ppg), the mitogen PHA, house dust mite extracts (Der p 1), and combinations. Treg cells (CD4+CD25(high) cells; intracellular forkhead/winged-helix family transcriptional repressor p3 [FOXP3] expression, FOXP3 levels, lymphocyte activation gene 3 mRNA expression, functional studies, and DNA methylation of the FOXP3 locus), proliferation, and T(H)2/T(H)1/T(H)17 cytokines were examined. RESULTS: Cord blood Treg cell counts (both unstimulated and PHA stimulated) were increased with maternal farming exposures and associated with higher FOXP3 (Der p 1 + Ppg stimulation) and trendwise higher lymphocyte activation gene 3 (Ppg) expression. Furthermore, Treg cell function was more efficient with farming exposure (effector cell suppression, P = .004). In parallel, T(H)2 cytokine (IL-5) levels were decreased and associated with decreased lymphoproliferation and increased IL-6 levels (Ppg stimulation, Der p 1 + Ppg stimulation, or both; P < .05). Maternal exposure to increasing numbers of farm animals and stables was discovered to exert distinct effects on Treg cells, T(H)1/T(H)2 cells, or both. Additionally, FOXP3 demethylation in offspring of mothers with farm milk exposure was increased (P = .02). CONCLUSIONS: Farm exposures during pregnancy increase the number and function of cord blood Treg cells associated with lower T(H)2 cytokine secretion and lymphocyte proliferation on innate exposure. One fascinating speculation is that maternal farm exposure might reflect a natural model of immunotherapy, potentially including a selection of innate stimuli in addition to allergen, shaping a child's immune system at an early stage.en
dc.language.isoenen
dc.subject.meshAdulten
dc.subject.meshAgricultureen
dc.subject.meshAnimalsen
dc.subject.meshAnimals, Domesticen
dc.subject.meshCohort Studiesen
dc.subject.meshCytokinesen
dc.subject.meshEnvironmental Exposureen
dc.subject.meshFemaleen
dc.subject.meshFetal Blooden
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshHumansen
dc.subject.meshInfant, Newbornen
dc.subject.meshLymphocyte Activationen
dc.subject.meshMaternal Exposureen
dc.subject.meshPregnancyen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshTh1 Cellsen
dc.subject.meshTh2 Cellsen
dc.titleMaternal farm exposure modulates neonatal immune mechanisms through regulatory T cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany. Bianca.Schaub@med.uni-muenchen.deen
dc.identifier.journalThe Journal of allergy and clinical immunologyen

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