Regulatory T cells in autoimmune primary adrenal insufficiency.

OXYGEN consumption; REGULATORY T cells; ADDISON'S disease; ADRENAL insufficiency; ADRENAL cortex; IMMUNOLOGICAL tolerance; AUTOIMMUNE diseases

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 naive and expanded Tregs in patients with PAI and polyendocrine syndromes compared to age- and gender-matched healthy controls. Flow cytometry was used to assess the frequency and characterize 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 were similar between patients and controls. 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. Regulatory T cells (Tregs) are involved in the initiation or progress of many autoimmune disorders. Here, we describe number and function of Tregs in the endocrine autoimmune disorder primary adrenal insufficiency (PAI). Tregs from PAI patients were adequate in number and in functional cell assays, but had an increase in mitochondria and killer receptors in transcriptomic assays, and showed a higher proliferation capacity, which might point to a higher turnover of these suppressive cells. Graphical Abstract [ABSTRACT FROM AUTHOR]

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