Dataset Information

Household size, T regulatory cell development, and early allergic disease: a birth cohort study.

ABSTRACT:

Background

Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally.

Objective

We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age.

Methods

A birth cohort (n = 1074) with information on prenatal and postnatal early life factors. Both naïve Treg (nTreg) and activated Treg (aTreg) cell populations (as a proportion of CD4⁺ T cells) were available in 463 infants at birth (cord blood), 600 at 6 months, and 675 at 12 months. 191 infants had serial measures. Measures of allergic status at 12 months were polysensitization (sensitization to 2 or more allergens), clinically proven food allergy, atopic eczema, and atopic wheeze.

Results

Infants born to larger households (3 or more residents) had higher longitudinal nTreg proportions over the first postnatal year with a mean difference (MD) of 0.67 (95% CI 0.30-1.04)%. Higher nTreg proportions at birth were associated with a reduced risk of infant allergic outcomes. Childcare attendance and breastfeeding were associated with higher longitudinal nTreg proportions (MD 0.48 (95% CI 0.08-0.80)%.

Conclusion

Multiple prenatal and postnatal microbial factors are associated with nTreg and aTreg development. Larger household size was associated with higher nTreg at birth which in turn was associated with reduced allergic sensitization and disease at 12 months of age.

SUBMITTER: Ponsonby AL

PROVIDER: S-EPMC9545943 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Household size, T regulatory cell development, and early allergic disease: a birth cohort study.

Ponsonby Anne-Louise AL Collier Fiona F O'Hely Martin M Tang Mimi L K MLK Ranganathan Sarath S Gray Lawrence L Morwitch Ellen E Saffery Richard R Burgner David D Dwyer Terence T Sly Peter D PD Harrison Leonard C LC Vuillermin Peter P

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20220601 6

<h4>Background</h4>Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally.<h4>Objective</h4>We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age.<h4>Methods</h4>A birth cohort (n = 1074) with information on prenatal and postnatal ea ...[more]

PMID: 35754137

Similar Datasets

Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.

Project description:BackgroundImmunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking.ObjectivesAs part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age.MethodsImmunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated.ResultsThe proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02).Conclusions and clinical relevanceThese findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.

Dataset Information

Household size, T regulatory cell development, and early allergic disease: a birth cohort study.

Background

Objective

Methods

Results

Conclusion

Publications

Household size, T regulatory cell development, and early allergic disease: a birth cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets