Rural environments boost immune systems in children

Key takeaways:

• Exposure to environmental factors early in life may impact immune system development.
• A better understanding of these mechanisms may lead to the development of interventions.

Children who were raised in rural environments with lots of time outdoors and some exposure to animals had immune systems that were better regulated than children raised in urban environments, according to a study published in Allergy.

These findings highlight the importance of the exposome on immune development early in life, Liam O’Mahony, PhD, professor of immunology in the departments of medicine and microbiology at APC Microbiome Ireland, University College Cork, and colleagues wrote.

“Our study found that many of the important environmental factors were linked with altered exposure to microbes during the first few years of a young child’s life, a crucial stage in shaping a person’s immune system as it is particularly responsive to environmental exposures including infections, nutrition and microbiome,” O’Mahony said in a press release.

Study design, results

The study comprised 150 children aged 15 to 35 months from the same ethnolinguistic AmaXhosa background in South Africa. It included 46 children with atopic dermatitis and 44 healthy children from rural areas and 33 children with AD and 27 healthy children from urban areas.

Using mRNA sequencing, the researchers identified 132 differentially expressed genes (DEGs) in the peripheral blood mononuclear cells (PBMCs) of the children with AD compared with the children who did not have AD.

Further analysis revealed a cluster of children from the urban group with similar transcriptomic landscapes and two subclusters in the rural group, Rural_1 and Rural_2, with no differences in age or gender between the groups.

Location drove these clusters instead of AD, indicating the impact that environmental and living conditions have on immune systems in growing children, the researchers wrote.

Exposures to animals and sunlight accounted for the most statistically significant differences between the rural and urban clusters.

Also, compared with the urban cluster, the Rural_1 group had a significantly higher rate of vaginal deliveries and Rural_2 had significantly lower rates of peanut and amasi consumption and differences in heating fuels.

Comparing DEGs between the clusters revealed distinct immune pathway enrichments, the researchers wrote, with the rural group overall having a much larger number of DEGs compared with the urban group.

Similarly, compared with the urban group, both rural groups had significant upregulation of multiple chemokines and chemokine receptors in PBMCs.

There was differential regulation in multiple G protein-coupled receptors (GPCRs) between the rural and urban groups. GPR132, which can be activated by microbiota-derived metabolites and is involved in the control of autoimmune responses, was the most significantly upregulated GPCR gene in the rural groups.

The rural groups also had significantly elevated levels of IL-1 receptor subtypes, suggesting higher levels of IL-1 signaling, in addition to significantly upregulated IL-10 gene expression compared with the urban group. The highest expression levels of IL-2 receptor subunits and genes related to TH17 signaling were found in the urban group.

Further, PBMCs from both rural groups had significantly upregulated inhibitory leukocyte immunoglobulin-like receptors.

There were significant differences in the expression levels of genes necessary for histamine synthesis, degradation and receptors between the rural and urban groups as well.

The researchers also found a gene co-expression community specific to the urban group that indicated metabolic compromise, with these pathways suggesting a unique pattern of PBMC metabolism.

The most significantly regulated pathways in Rural_1 were related to the innate activation of the immune system, cytokine and chemokine signaling, changes in lymphocyte polarization and immune cell metabolism. In Rural_2, the gene co-expression community suggested ongoing lymphocyte activation with changes in immune cell survival and proliferation.

Conclusions

Based on these findings, the researchers said that there may be a transition from a truly rural gene expression signature represented by Rural_1 to an intermediate gene expression signature in Rural_2 to the urban pattern of immune cell gene expression.

However, the researchers cautioned that outdoor pollution levels, dietary habits and other factors that were not assessed in this study may drive differences in gene expression between the rural subgroups as well.

With the higher level of immunoregulatory pathway activation in rural children compared with the urban children, the researchers said that early life environmental exposures and lifestyle factors are the predominant influences on the peripheral blood immune transcriptome in children.

“This ‘immunological window of opportunity’ plays a critical role in establishing the limitations and reaction trajectories of our immune system that stay with us for life and influence the risk of immune-mediated diseases,” O’Mahony said.

By understanding these mechanisms, the researchers wrote, therapies for preventing chronic immune-mediated disorders may be possible, in addition to the development of novel diagnostic markers and translational targets.

“Growing our understanding of the mechanisms and role of environment on immune development is highly important, and research such as this can help pave the way for new developments in early disease diagnosis and expediting interventions for more specific and safe modulation of immune activity,” he said.

Reference:

• Rural environment supports children’s immune systems. https://www.ucc.ie/en/news/2023/rural-environment-supports-childrens-immune-systems.html. Published Aug. 3, 2023. Accessed Aug. 15, 2023.