Aging Selectively Alters PRR and ISG Expression in Endo- and Ecto-Cervical Stromal Fibroblasts From the Human Female Reproductive Tract.

Problem: Aging alters immune function in women and can lead increased risk of infections, particularly in the female reproductive tract (FRT).

Method Of Study: To determine how aging affects innate immune responses in the cervical stroma of the FRT, we isolated endocervical (CX) and ectocervical (ECX) stromal fibroblasts and determine if their expression of multiple pattern recognition receptors (PRRs) and responses to viral stimulation varied with menopause and age.

Results: Constitutive expression of most PRRs did not vary with age or menopausal status in either cell type.

Sex Hormones and Aging Modulate Interferon Lambda 1 Production and Signaling by Human Uterine Epithelial Cells and Fibroblasts.

Estradiol (E) and progesterone (P) have potent effects on immune function in the human uterine endometrium which is essential for creating an environment conducive for successful reproduction. Type III/lambda (λ) interferons (IFN) are implicated in immune defense of the placenta against viral pathogens, which occurs against the backdrop of high E and P levels. However, the effect of E and P in modulating the expression and function of IFNλ1 in the non-pregnant human uterine endometrium is unknown.

Neutrophil extracellular traps prevent HIV infection in the female genital tract.

Women acquire human immunodeficiency virus (HIV) mainly through sexual intercourse. However, low transmission rates per sexual act indicate that local immune mechanisms contribute to HIV prevention. Neutrophils represent 10-20% of the genital immune cells in healthy women.

Isolation of Dendritic Cells from the Human Female Reproductive Tract for Phenotypical and Functional Studies.

The characterization of the human dendritic cells (DCs) resident in mucosal tissues is challenging due to the difficulty in obtaining samples, and the low numbers of DCs present per tissue. Yet, as the phenotype and function of DCs is modified by the tissue environment, it is necessary to analyze tissue resident DC populations, since blood derived DCs incompletely reflect the complexities of DCs in tissues. Here we present a protocol to isolate DCs from the human female reproductive tract (FRT) using hysterectomy specimens that allows both phenotypical and functional analyses.

Aging impacts CD103 CD8 T cell presence and induction by dendritic cells in the genital tract.

As women age, susceptibility to systemic and genital infections increases. Tissue-resident memory T cells (TRMs) are CD103 CD8 long-lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8 T cells.

Menopausal status influences the expression of programmed death (PD)-1 and its ligand PD-L1 on immune cells from the human female reproductive tract.

Problem: The programmed death 1 (PD-1)/PD-L1 pathway regulates peripheral tolerance, immune responses, and is up-regulated in chronic viral infections, including HIV infection. However, expression of PD-1/PD-L1 on immune cells from the human female reproductive tract (FRT) and possible regulation by menopause and sex hormones are poorly understood.

Method Of Study: PD-1/PD-L1 expression was analyzed on CD4(+) and CD8(+) T cells, CD163(+) macrophages, and CD11c(+) dendritic cells (DC) from endometrium (EM), endocervix (CX) and ectocervix (ECX).

Estradiol reduces susceptibility of CD4+ T cells and macrophages to HIV-infection.

The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-β-estradiol (E2) and ethinyl estradiol (EE) in HIV-infection of CD4(+) T-cells and macrophages.

Disruption of histone modification and CARM1 recruitment by arsenic represses transcription at glucocorticoid receptor-regulated promoters.

Chronic exposure to inorganic arsenic (iAs) found in the environment is one of the most significant and widespread environmental health risks in the U.S. and throughout the world.