Changes in DNA Methylation from Age 18 to Pregnancy in Type 1, 2, and 17 T Helper and Regulatory T-Cells Pathway Genes

Abstract

To succeed, pregnancies need to initiate immune biases towards T helper 2 (Th2) responses, yet little is known about what establishes this bias. Using the Illumina 450 K platform, we explored changes in DNA methylation (DNAm) of Th1, Th2, Th17, and regulatory T cell pathway genes before and during pregnancy. Female participants were recruited at birth (1989), and followed through age 18 years and their pregnancy (2011–2015). Peripheral blood DNAm was measured in 245 girls at 18 years; from among these girls, the DNAm of 54 women was repeatedly measured in the first (weeks 8–21, n = 39) and second (weeks 22–38, n = 35) halves of pregnancy, respectively. M-values (logit-transformed β-values of DNAm) were analyzed: First, with repeated measurement models, cytosine–phosphate–guanine sites (CpGs) of pathway genes in pregnancy and at age 18 (nonpregnant) were compared for changes (p ≤ 0.05). Second, we tested how many of the 348 pathway-related CpGs changed compared to 10 randomly selected subsets of all other CpGs and compared to 10 randomly selected subsets of other CD4+-related CpGs (348 in each subset). Contrasted to the nonpregnant state, 27.7% of Th1-related CpGs changed in the first and 36.1% in the second half of pregnancy. Among the Th2 pathway CpGs, proportions of changes were 35.1% (first) and 33.8% (second half). The methylation changes suggest involvement of both Th1 and Th2 pathway CpGs in the immune bias during pregnancy. Changes in regulatory T cell and Th17 pathways need further exploration.

Cigarette smoke-induced alterations in blood: A review of research on DNA methylation and gene expression.

“…Compared to the prior systematic review (Gao et al, 2015), we report 254 common, but 1,504 unique genes. Further, this review identified enrichment of the AHR and Th1/Th2 pathways among smokers compared to nonsmokers, a finding that has been previously observed in other studies (Iqbal et al, 2018; Ma & Li, 2017; Strzelak, Ratajczak, Adamiec, & Feleszko, 2018). A key difference from these earlier studies is that we expand on previous research by integrating both transcriptomic and methylation studies.…”

Thymus-Derived Regulatory T Cells Exhibit Foxp3 Epigenetic Modification and Phenotype Attenuation after Mating in Mice

“…Changes in T cell methylation state have been suggested in women experiencing recurrent miscarriage, in which decidua tissue showed greater methylation of the FOXP3 locus compared with women with healthy pregnancies (91). Analysis of 348 CpG sites in PBMC before and during pregnancy demonstrated altered methylation in several genes associated with Th1, Th2, Th17, and Treg phenotypes, including sites within the CTLA4 and FOXP3 loci (92). However, a limitation of both studies is that isolated T cell populations were not used, so Treg-specific methylation or stability of FOXP3 expression cannot be inferred.…”

Cohort Profile Update: The Isle of Wight Whole Population Birth Cohort (IOWBC)

“…1 Changes in DNA-methylation from age 18 to pregnancy: Changes in DNA-methylation of Th1, Th2, Th17, and regulatory T cell pathway genes were found before and during pregnancy and these methylation changes were suggestive of involvement of both Th1 and Th2 pathways. [11] 2 DNA-methylation during puberty, young adulthood, and pregnancy: A higher consistency in DNA-methylation was observed during puberty (10 to 18 years) and between age 18 years to early pregnancy while there was low consistency/stability between early and late pregnancy in the same individual, indicating that pregnancy is a time of dynamic change. [12] 3 Filaggrin gene expression at birth and eczema risk in infancy: Filaggrin gene (FLG) expression in umbilical cord blood was associated with eczema development in infancy, suggesting that early identification of infants at increased risk of eczema is possible.…”