Regulation of TH17 markers early in life through maternal farm exposure

Background Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by T H 1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as T H 17 cells, influenced by genetic predisposition. Objective We examined the role of maternal farm exposure and genetic predisposition on T H 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. T H 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. T H 17/Treg/T H 1/T H 2 cytokines and 7 single nucleotide polymorphisms within the T H 17 lineage ( RORC , IL23R , and IL17 ) were examined. Results T H 17 lineage mRNA markers were expressed at birth at low concentrations independent of maternal farm exposure. A positive correlation between T H 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 T H 17 lineage genes influenced gene expression of T H 17 and Treg cell markers and cytokine secretion. Conclusions Gene expression of T H 17 lineage markers in cord blood was not influenced by maternal farming. Yet T H 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 T H 17 immune maturation, potentially regulating the development of immune-mediated diseases, such as childhood asthma.