Details

Autor(en) / Beteiligte

• Lluis, Anna, PhD
• Ballenberger, Nikolaus, PhD
• Illi, Sabina, PhD
• Schieck, Maximilian, MSc
• Kabesch, Michael, MD
• Illig, Thomas, PhD
• Schleich, Isolde
• von Mutius, Erika, MD, MSc
• Schaub, Bianca, MD

Titel

Regulation of TH 17 markers early in life through maternal farm exposure

Ist Teil von

• Journal of allergy and clinical immunology, 2013, Vol.133 (3), p.864-871

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Background Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by TH 1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as TH 17 cells, influenced by genetic predisposition. Objective We examined the role of maternal farm exposure and genetic predisposition on TH 17 cell responses to innate and adaptive immune stimulation in cord blood. Methods Eighty-four pregnant mothers were recruited before delivery. Detailed questionnaires (60 nonfarming mother, 22 farming mothers, and 2 exclusions) assessed farming exposures. Cord blood was stimulated with lipid A, peptidoglycan (Ppg), or PHA. TH 17 lineage (retinoic acid receptor–related orphan receptor C [RORC] , retinoic acid receptor–related orphan receptor α [RORA] , IL-23 receptor [IL23R] , IL17 , IL17F , and IL22 ) and Treg cell markers (forkhead box protein 3 [FOXP3] , lymphocyte activation gene 3 [LAG3] , and glucocorticoid-induced TNF receptor [GITR] ) were assessed at the mRNA level. TH 17/Treg/TH 1/TH 2 cytokines and 7 single nucleotide polymorphisms within the TH 17 lineage ( RORC , IL23R , and IL17 ) were examined. Results TH 17 lineage mRNA markers were expressed at birth at low concentrations independent of maternal farm exposure. A positive correlation between TH 17 lineage markers and FOXP3 (mRNA) was observed on stimulation (nonfarming mothers: lipid A, Ppg, and PHA; farming mothers: Ppg and PHA), influenced by maternal farming. Specific single nucleotide polymorphisms within the TH 17 lineage genes influenced gene expression of TH 17 and Treg cell markers and cytokine secretion. Conclusions Gene expression of TH 17 lineage markers in cord blood was not influenced by maternal farming. Yet TH 17 and Treg cell markers were positively correlated and influenced by maternal farm exposure. Our data suggest that prenatal exposures and genetic predisposition play a role during early TH 17 immune maturation, potentially regulating the development of immune-mediated diseases, such as childhood asthma.