Regulatory T cells in autoimmune primary adrenal insufficiency.

Primary adrenal insufficiency (PAI) is most often caused by an autoimmune destruction of the adrenal cortex resulting in failure to produce cortisol and aldosterone. The aetiology is thought to be a combination of genetic and environmental risk factors, leading to breakdown of immunological tolerance. Regulatory T cells (Tregs) are deficient in many autoimmune disorders, but it is not known whether they contribute to development of PAI. We aimed to investigate the frequency and function of naïve and expanded Tregs from patients with PAI and polyendocrine syndromes compared to age- and gender-matched healthy controls. Flow cytometry was used to assess the frequency and characterise functional markers of blood Tregs in PAI (N=15). Expanded Treg suppressive abilities were assessed with a flow cytometry based suppression assay (N=20), while bulk RNA-sequencing was used to examine transcriptomic differences (N=16) and oxygen consumption rate was measured by a Seahorse cell metabolic assay (N=11). Our results showed that Treg frequency and suppressive capacity was similar between patients and control. An increased expression of killer-cell leptin-like receptors and mitochondrial genes was revealed in PAI patients, but their expanded Tregs did not display signs of mitochondrial dysfunction. Our findings do not support a clear role for Tregs in the contribution of PAI development.