Abstract
Inflammatory responses are characterized by the activation of immune cells, while inflammatory biomarkers intricately interact with the immune system. While experimental studies have provided important mechanistic insights, large community-based investigations jointly profiling immune cell phenotypes and inflammatory biomarkers remain limited. This study aims to investigate the association between circulating immune cell phenotypes and inflammatory protein biomarkers in the Framingham Heart Study Offspring cohort. A sample of 873 dementia-free participants (52% female, mean age 61) had extensive profiling of peripheral blood mononuclear cells and inflammatory plasma protein biomarkers (OLINK Proteomics) collected at Offspring Exam 7 (the seventh examination cycle of the cohort, 1998 to 2001). Among cross-sectional pairwise associations between 77 immune cell phenotypes and 68 inflammatory biomarkers, CD8 naïve T cells showed negative associations with multiple inflammatory proteins, including CD40, CD5, CXCL9, CXCL10, IL8, OPG, TGF-alpha, TNF, TNFRSF9, and 4E-BP1. Higher levels of CD8 Cytotoxic T cells, CD8 + CD27-, CD8 effector T cells, and interferon gamma-producing CD8 T cells (Tc1) were all associated with higher levels of soluble CD8 alpha chain (CD8A). In contrast, CD4/CD8 T cell ratio, Immunoglobulin D (IgD)-expressing B cells and naïve Immunoglobulin D and Immunoglobulin M double-positive B cells (IgD + IgM + B cells) were associated with lower CD8A. Stratified analyses revealed significant associations primarily in males and participants over 60. These findings provide a comprehensive population-level characterization of the relationships between circulating immune cell phenotypes and inflammatory biomarkers in a well-defined community-based cohort, offering insight into immune cell-inflammatory profiles associated with aging.
Data availability
Framingham Heart Study Offspring data are available for request via NHLBI Biological Specimen and Data Repositories Information Coordinating Center (BioLINCC) (https:/biolincc.nhlbi.nih.gov/studies/framoffspring) .
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Acknowledgements
The authors thank the Framingham Heart Study participants, as well as the study team for their contributions.
Funding
This work was supported by the National Institutes of Health R01AG067457, and by NIH Research Grant 1F99AG095040-01 funded by the Office of Data Science Strategy (ODSS). Support for collection of FHS data was provided by the National Heart, Lung, and Blood Institute (contract number 75N92019D00031, 75N9202500012).
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JC performed data curation, formal analysis, investigation, and visualization, wrote the original draft and wrote for revisions and editing. MFD, KLL, and JMM performed conceptualization, funding acquisition, data curation, investigation, and visualization, wrote the original draft, and wrote revisions and editing. YC, SI, and AAYR performed the investigation and wrote for review and editing.
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Chen, J., Doyle, M.F., Cao, Y. et al. Circulating immune cell phenotypes are associated with inflammatory biomarkers in dementia-free participants from the Framingham Heart Study Offspring cohort. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41423-4
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DOI: https://doi.org/10.1038/s41598-026-41423-4
