Aging beyond menopause selectively decreases CD8+ T cell numbers but enhances cytotoxic activity in the human endometrium

Shen, Zheng; Patel, Mickey V.; Rodriguez-García, Marta; Wira, Charles R.

doi:10.1186/s12979-022-00312-w

Cited by 5 publications

(6 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the cytokine environment during antigen presentation is known to determine the function of induced T cells, this postmenopausal environment might support enhanced cytotoxic activity in CD8 + T cells after menopause. This would be congruent with our previous observations that cytotoxic activity of FRT CD8 + T cells is increased in postmenopausal women [10][11][12][13]. Further, our studies suggest enhanced induction of Th2 differentiation following menopause.…”

Section: Discussionsupporting

confidence: 93%

“…Thus, it is critical to understand how the immune system changes in the FRT before and after menopause as women age. We have previously described how menopause and aging induce multiple changes in immune cell distribution and function of different immune cells in the FRT, including Th17 cells, CD8 + T cells and dendritic cells (DCs) [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background Immune function in the genital mucosa balances reproduction with protection against pathogens. As women age, genital infections, and gynecological cancer risk increase, however, the mechanisms that regulate cell-mediated immune protection in the female genital tract and how they change with aging remain poorly understood. Unconventional double negative (DN) T cells (TCRαβ + CD4-CD8-) are thought to play important roles in reproduction in mice but have yet to be characterized in the human female genital tract. Using genital tissues from women (27–77 years old), here we investigated the impact of aging on the induction, distribution, and function of DN T cells throughout the female genital tract. Results We discovered a novel site-specific regulation of dendritic cells (DCs) and unconventional DN T cells in the genital tract that changes with age. Human genital DCs, particularly CD1a + DCs, induced proliferation of DN T cells in a TFGβ dependent manner. Importantly, induction of DN T cell proliferation, as well as specific changes in cytokine production, was enhanced in DCs from older women, indicating subset-specific regulation of DC function with increasing age. In human genital tissues, DN T cells represented a discrete T cell subset with distinct phenotypical and transcriptional profiles compared to CD4 + and CD8 + T cells. Single-cell RNA and oligo-tag antibody sequencing studies revealed that DN T cells represented a heterogeneous population with unique homeostatic, regulatory, cytotoxic, and antiviral functions. DN T cells showed relative to CD4 + and CD8 + T cells, enhanced expression of inhibitory checkpoint molecules and genes related to immune regulatory as well as innate-like anti-viral pathways. Flow cytometry analysis demonstrated that DN T cells express tissue residency markers and intracellular content of cytotoxic molecules. Interestingly, we demonstrate age-dependent and site-dependent redistribution and functional changes of genital DN T cells, with increased cytotoxic potential of endometrial DN T cells, but decreased cytotoxicity in the ectocervix as women age, with implications for reproductive failure and enhanced susceptibility to infections respectively. Conclusions Our deep characterization of DN T cell induction and function in the female genital tract provides novel mechanistic avenues to improve reproductive outcomes, protection against infections and gynecological cancers as women age.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…69 The endometrium of postmenopausal women had significantly higher production of TNFα by CD8 + cells, which was exclusively regulated by estradiol and not progesterone. 68 The visceral fat of postmenopausal compared to premenopausal women had higher frequency of effector memory and exhausted CD8 + T cells. Similar trends were found for CD4 + cells: postmenopausal women had significantly higher numbers of central memory, senescent, and exhausted CD4 + T cells.…”

Section: Ob E S It Y In Female Mice and Humansmentioning

confidence: 96%

“…Although Tregs in blood increase with age in premenopausal women, they sharply decrease postmenopausally to perhaps explain the higher TNFα/IL-10 ratio in postmenopausal women. 67 In addition to supporting the accumulation of (often) more inflamed visceral adipose tissue, menopause increases inflammation in the endometrium from resident and nonresident CD8 + cells, despite reduction of total CD8 + numbers, 68 and similar to increases in the VAT of postmenopausal women. 69 The endometrium of postmenopausal women had significantly higher production of TNFα by CD8 + cells, which was exclusively regulated by estradiol and not progesterone.…”

Section: Ob E S It Y In Female Mice and Humansmentioning

confidence: 99%

T cells in obesity‐associated inflammation: The devil is in the details

Valentine,

Nikolajczyk

2024

Immunological Reviews

View full text Add to dashboard Cite

SummaryObesity presents a significant health challenge, affecting 41% of adults and 19.7% of children in the United States. One of the associated health challenges of obesity is chronic low‐grade inflammation. In both mice and humans, T cells in circulation and in the adipose tissue play a pivotal role in obesity‐associated inflammation. Changes in the numbers and frequency of specific CD4+ Th subsets and their contribution to inflammation through cytokine production indicate declining metabolic health, that is, insulin resistance and T2D. While some Th subset alterations are consistent between mice and humans with obesity, some changes mainly characterize male mice, whereas female mice often resist obesity and inflammation. However, protection from obesity and inflammation is not observed in human females, who can develop obesity‐related T‐cell inflammation akin to males. The decline in female sex hormones after menopause is also implicated in promoting obesity and inflammation. Age is a second underappreciated factor for defining and regulating obesity‐associated inflammation toward translating basic science findings to the clinic. Weight loss in mice and humans, in parallel with these other factors, does not resolve obesity‐associated inflammation. Instead, inflammation persists amid modest changes in CD4+ T cell frequencies, highlighting the need for further research into resolving changes in T‐cell function after weight loss. How lingering inflammation after weight loss affecting the common struggle to maintain lower weight is unknown. Semaglutide, a newly popular pharmaceutical used for treating T2D and reversing obesity, holds promise for alleviating obesity‐associated health complications, yet its impact on T‐cell‐mediated inflammation remains unexplored. Further work in this area could significantly contribute to the scientific understanding of the impacts of weight loss and sex/hormones in obesity and obesity‐associated metabolic decline.

show abstract

“…Additionally, changes in T cell function and a decline in their diversity and responsiveness have been observed during menopause. These alterations in immune cell function can aff ect the overall immune response and increase the risk of immune-related disorders [60].…”

Section: Alterations In Immune Cell Functionmentioning

confidence: 99%

The Art of Psychoneuroimmunology in Menopause Management

Anurogo

2023

J Biomed Res Environ Sci

View full text Add to dashboard Cite

Psychoneuroimmunology is a field that explores the intricate connections between the mind, brain, and immune system. This narrative review integrates various aspects of psychoneuroimmunology in the context of menopause. It highlights the hormonal changes during menopause, their impact on psychological well-being and the immune system, as well as the psychological aspects of menopause such as emotional changes, cognitive functioning, and sleep disturbances. The immunological changes during menopause, including alterations in immune cell function and cytokine production, are discussed along with their influence on psychological well-being. This comprehensive review emphasizes the bidirectional communication between the brain and immune system, the effects of hormonal, psychological, and immunological factors on each other, and the role of chronic inflammation in menopause-related psychological symptoms. Additionally, it explores the influence of psychosocial factors like stress and social support on menopausal symptoms, and presents various psychoneuroimmunology interventions such as mind-body techniques, pharmacological options, and lifestyle modifications. The importance of integrating psychoneuroimmunology approaches in menopause research, potential areas for further investigation, and the call for comprehensive strategies to improve menopausal care are also highlighted, underscoring the significance of this interdisciplinary field in understanding and enhancing menopausal health and well-being.

show abstract

Aging beyond menopause selectively decreases CD8+ T cell numbers but enhances cytotoxic activity in the human endometrium

Cited by 5 publications

References 58 publications

Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa

Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa

T cells in obesity‐associated inflammation: The devil is in the details

The Art of Psychoneuroimmunology in Menopause Management

Contact Info

Product

Resources

About