A blunted TH17 cytokine signature in women with mild cognitive impairment: insights from inflammatory profiling of a community-based cohort of older adults

Bachstetter, Adam D; Lutshumba, Jenny; Winford, Edric; Abner, Erin L; Martin, Barbra J; Harp, Jordan P; Van Eldik, Linda J; Schmitt, Frederick A; Wilcock, Donna M; Stowe, Ann M; Jicha, Gregory A; Nikolajczyk, Barbara S

doi:10.1093/braincomms/fcad259

Cited by 3 publications

(2 citation statements)

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“…30–32 There are reports of functional differences in T cells between men and women in renal cell carcinoma, 33 HIV, 34 COVID-19, 35 and dementia-associated diseases. 36 Utilizing a PCR array approach, we observed many significantly changed genes in the renal T cells due to sex and salt. Of particular interest is Ccl4 , which is a chemokine-encoding gene associated with immune system modulation.…”

Section: Discussionmentioning

confidence: 92%

Sex-Dependency of T Cell-Induced Salt-Sensitive Hypertension and Kidney Damage

Abais-Battad,

Dasinger,

Lund

et al. 2024

Hypertension

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BACKGROUND: It is established that the immune system, namely T cells, plays a role in the development of hypertension and renal damage in male Dahl salt-sensitive (SS) rats, but far less is known about this relationship in females. Rats with genetically deleted T cells via CD247 gene mutation on the Dahl SS background (SS CD247−/− ) were utilized to interrogate the effect of sex and T cells on salt sensitivity. METHODS: We assessed the hypertensive and kidney injury phenotypes in male versus female SS and SS CD247−/− rats challenged with 3 weeks of high salt (4.0% NaCl). Differences in T-cell activation genes were examined in renal T cells from male and female SS rats, and a sex-specific adoptive transfer was performed by injecting male or female splenocytes into either male or female SS CD247−/− recipients to determine the potential contribution of T-cell sex. RESULTS: The lack of functional T cells in SS CD247−/− rats significantly reduced salt-induced hypertension and proteinuria in both sexes, although SS CD247−/− females exhibited greater protection from kidney damage. Adoptive transfer of either Dahl SS male or female splenocytes into SS CD247−/− male recipients exacerbated hypertension and proteinuria compared with controls, while in SS CD247−/− female recipients, exacerbation of disease occurred only upon transfer of male, but not female, SS splenocytes. CONCLUSIONS: The absence of T cells in the SS CD247−/− normalized sex differences in blood pressure, though sex differences in renal damage persisted. Splenocyte transfer experiments demonstrated that salt sensitivity is amplified if the sex of the T cell or the recipient is male.

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Section: Discussionmentioning

confidence: 92%

Sex-Dependency of T Cell-Induced Salt-Sensitive Hypertension and Kidney Damage

Abais-Battad,

Dasinger,

Lund

et al. 2024

Hypertension

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“…The participants in this study were recruited from a larger cohort study of aging and dementia at the University of Kentucky Alzheimer’s Disease Research Center [ 20 , 21 ]. Before participating in the study, the participants provided informed consent according to University of Kentucky Institutional Review Board-approved protocols.…”

Section: Methodsmentioning

confidence: 99%

Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort

Winford,

Lutshumba,

Martin

et al. 2024

Immun Ageing

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Background and purpose The immune response changes during aging and the progression of Alzheimer’s disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults. Methods Study participants from a University of Kentucky Alzheimer’s Disease Research Center (UK-ADRC) community-based cohort of aging and dementia were used to test our hypothesis. There were 84 participants, 44 women and 40 men. Participants underwent physical examination, neurological examination, medical history, cognitive testing, and blood collection to determine plasma biomarker levels (Aβ42/Aβ40 ratio, total tau, Neurofilament Light chain (Nf-L), Glial Fibrillary Acidic Protein (GFAP)) and to isolate peripheral blood mononuclear cells (PBMCs). Flow cytometry was used to analyze PBMCs from study participants for effector and memory T cell populations, including CD4+ and CD8+ central memory T cells (TCM), Naïve T cells, effector memory T cells (TEM), and effector memory CD45RA+ T cells (TEMRA) immune cell markers. Results CD8+ TEMRAs were positively correlated with Nf-L and GFAP. We found no significant difference in CD8+ TEMRAs based on cognitive scores and no associations between CD8+ TEMRAs and AD-related biomarkers. CD4+ TEMRAs were associated with cognitive impairment on the MMSE. Gender was not associated with TEMRAs, but it did show an association with other T cell populations. Conclusion These findings suggest that the accumulation of CD8+ TEMRAs may be a response to neuronal injury (Nf-L) and neuroinflammation (GFAP) during aging or the progression of AD and ADRD. As our findings in a community-based cohort were not clinically-defined AD participants but included all ADRDs, this suggests that TEMRAs may be associated with changes in systemic immune T cell subsets associated with the onset of pathology.

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