Role of androgen receptor signaling in the activation and differentiation of plasmacytoid dendritic cells

Sammanfattning: Androgens are steroid hormones essential for the development and maintenance of male reproductive organs and secondary sexual characteristics. Plasmacytoid dendritic cells (pDCs) are immune cells that act as the first line of defense against viral infections. These cells have specialized receptors such as the toll-like receptors (TLR7) that recognize viral nucleic acids and initiate the production of antiviral cytokines such as Type I interferons (IFN-α1 and IFN-α2). Androgen receptor signaling might affect pDC functions throughout their activation and maturation in response to viral infections via the androgen receptor (AR), a nuclear hormone receptor that binds to hormones such as testosterone, an androgen hormone. Androgens have also been shown to promote the replication and intensity of some viruses, most notably SARS-CoV-2, an RNA virus. Understanding the mechanism of androgen signaling is critical for developing effective antiviral therapies. Considering this, we stimulated human peripheral mononuclear cells (PBMCs) with a TLR7 agonist such as Gardiquimod, an AR agonist R1881, and the synthetic androgen named Testosterone propionate. An antagonist namely G15 for the G-protein coupled estrogen receptor was also used. These compounds are used to activate the AR in order to assess its role in interferon production. Furthermore, qPCR was used to examine the gene expression of IFN⍺1, IFN⍺2, IRF7, and MX1 using GAPDH as the endogenous control. Flow cytometry was also performed after the cells were stained with BDCA2, CD3, CD19, CD123, and IFN⍺2 to evaluate the pDC population and interferon production. The findings showed an increase in IFN response when the PBMCs were stimulated with Gardiquimod and the agonists, with individual differences. To date, relatively few studies have been conducted on the role of androgens in immune system regulation. Further research can generate effective treatment targets and lessen the impact that certain infections have on human health.