Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells - 15/08/11
, Jing Liu, MD a, b, , Sabine Höppler a, Isolde Schleich a, Jochen Huehn, MD c, Sven Olek, PhD d, Georg Wieczorek, PhD d, Sabina Illi, PhD a, Erika von Mutius, MD aReprint requests: Bianca Schaub, MD, University Children’s Hospital Munich, Dr von Haunersches Kinderspital, Lindwurmstr 4, 80337 Munich, Germany.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 TH2-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+CD25high 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 TH2/TH1/TH17 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, TH2 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, TH1/TH2 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 TH2 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.
Le texte complet de cet article est disponible en PDF.Key words : Cord blood, cytokines, farming, innate, interleukin, methylation, microbial, T regulatory cells, Toll-like receptor
Abbreviations used : CBMC, CT, FITC, FOXP3, GITR, LAG3, Ppg, TLR, Treg, TSDR
Plan
| Supported by Stiftung OMNIBUS, Friedrich-Baur Institut, Münchner Universitätsgesellschaft, Bayerische Forschungsstiftung (PIZ-140-08) (B.S.), and DFG SFB650 (J.H.). |
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| Disclosure of potential conflict of interest: S. Olek is an employee and stockholder of Epiontis. The rest of the authors have declared that they have no conflict of interest. |
Vol 123 - N° 4
P. 774 - avril 2009 Retour au numéro
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