Association between serum folate and T cell subsets in a population-based study

TL;DR

This study explores how serum folate levels relate to different types of T cells in a population, suggesting a possible link between folate and immune health.

Contribution

The paper presents new population-based evidence on the associations between serum folate and specific CD8+ T cell subsets.

Findings

Higher folate levels were positively associated with Effector Memory CD8+ T cells and certain CD8+ T cell subtypes.

Lower folate levels were linked to fewer Central Memory and naïve CD8+ T cells.

Findings were not statistically significant after multiple testing but were supported by sensitivity analyses.

Abstract

Folate, also called vitamin B9, plays a key role in various cellular processes that support T cell proliferation and function, which in turn regulate adaptive immune responses. Nonetheless, the associations between serum folate concentrations and specific T cell subsets remain underexplored.

Data of the population-based MEIA study were analyzed including 594 participants aged 19–75 years in Augsburg study region, Germany. Serum folate concentrations were measured (right-censored at 20 ng/mL) and immunophenotyping of T cells via flow cytometry was performed in fresh blood samples. Associations between folate concentrations and T cell subsets were analyzed using a multivariable two-stage regression model to account for censoring.

Positive associations were noted with Effector Memory CD8 + T cells (\documentclass[12pt]{minimal}
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\begin{document}$$\:\beta\:$$\end{document}= 0.39; 95% CI [0.09;0.70]), CD8+ CD27- CD28+ T cells (\documentclass[12pt]{minimal}
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\begin{document}$$\:\beta\:$$\end{document}= 1.02; 95% CI [1.00; 1.03]), and CD8+ CD27+ CD28- T cells (\documentclass[12pt]{minimal}
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\begin{document}$$\:\beta\:$$\end{document}= 1.01; 95% CI [1.00; 1.03]), negative associations were observed with Central Memory CD8+ T cells (\documentclass[12pt]{minimal}
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\begin{document}$$\:\beta\:$$\end{document}= − 0.29; 95% CI [− 0.47; − 0.10]) and naïve CD8+ T cells (\documentclass[12pt]{minimal}
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\begin{document}$$\:\beta\:$$\end{document}= − 0.33; 95% CI [− 0.63; − 0.04]). Although these associations did not retain statistical significance after adjustment for multiple testing, they were fully supported by sensitivity analyses.

This study provides preliminary evidence linking serum folate to specific T cell subsets, particularly within CD8 + populations. While findings are suggestive, they emphasize the potential importance of adequate folate levels for immune health. Further longitudinal and interventional studies are needed to confirm these associations and explore the role of folate in immune function.

The online version contains supplementary material available at 10.1007/s00394-025-03872-x.

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