ArticleImmunity & ageing : I & A2023
Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa.
Article in Immunity & ageing : I & A, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Ovarian localization drives IL-7R-dependent CD8 coreceptor expression in peripheral double-negative T cells.Cellular and molecular life sciences : CMLS · 2026Article
- Mucosal Dynamics Contributing to Innate Immune Responses to HIV in the Human Female Genital Tract.Viruses · 2026Review
- Enumeration, Phenotyping, and Clinical Associations of Tissue-Resident T Cells in the Ecto- and Endocervix of Women Attending a Colposcopy Clinic.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Spatial and functional diversity of innate lymphoid cells in the human female genital tract may contribute to antiviral responses to HIV.Nature immunology · 2025Article
- Regulatory Interplay of p53, AMPK, and mTOR in Decidualization: Implications for Reproductive Competence and Cancer Biology.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Decoding functional and developmental trajectories of tissue-resident uterine dendritic cells through integrative omics.iScience · 2025Article
- Endometrial Aging and Reproductive Decline: The Central Role of Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Aging Is Associated With Decreased Lactobacillus and Increased Cervicovaginal Inflammation in Canadian Women.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- Sialylation-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in uterine corpus endometrial carcinoma.Cancer cell international · 2024Article
- Human genital dendritic cell heterogeneity confers differential rapid response to HIV-1 exposure.Frontiers in immunology · 2024Article
- Increases in the susceptibility of human endometrial CD4Frontiers in immunology · 2024Article
- Impact of aging on the frequency, phenotype, and function of CD4+ T cells in the human female reproductive tract.Frontiers in immunology · 2024Article
- Development and validation of a nomogram for predicting overall survival in patients with early-onset endometrial cancer.BMC cancer · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundImmune 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.
resultsWe 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.
conclusionsOur 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.
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