{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:05:54Z","timestamp":1782821154620,"version":"3.54.5"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Western Norway Health Authorities"},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["103302"],"award-info":[{"award-number":["103302"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2005=\u200515). Expanded Treg suppressive abilities were assessed with a flow cytometry based suppression assay (N\u2005=\u200520), while bulk RNA-sequencing was used to examine transcriptomic differences (N\u2005=\u200516) and oxygen consumption rate was measured by a Seahorse cell metabolic assay (N\u2005=\u200511). 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.<\/jats:p>","DOI":"10.1093\/cei\/uxad087","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T12:29:56Z","timestamp":1691756996000},"page":"47-57","source":"Crossref","is-referenced-by-count":5,"title":["Regulatory T cells in autoimmune primary adrenal insufficiency"],"prefix":"10.1093","volume":"215","author":[{"given":"Thea","family":"Sj\u00f8gren","sequence":"first","affiliation":[{"name":"Endocrine Medicine Group, Department of Clinical Science, University of Bergen , Bergen , Norway"},{"name":"Department of Medicine, Haukeland University Hospital , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Inge","family":"Bjune","sequence":"additional","affiliation":[{"name":"Center for Diabetes Research, Department of Clinical Science, University of Bergen , Bergen , Norway"},{"name":"Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen , Bergen , Norway"},{"name":"Hormone Laboratory, Haukeland University Hospital , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eystein S","family":"Husebye","sequence":"additional","affiliation":[{"name":"Endocrine Medicine Group, Department of Clinical Science, University of Bergen , Bergen , Norway"},{"name":"Department of Medicine, Haukeland University Hospital , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bergithe E","family":"Oftedal","sequence":"additional","affiliation":[{"name":"Endocrine Medicine Group, Department of Clinical Science, University of Bergen , Bergen , Norway"},{"name":"Department of Medicine, Haukeland University Hospital , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8485-2248","authenticated-orcid":false,"given":"Anette S B","family":"Wolff","sequence":"additional","affiliation":[{"name":"Endocrine Medicine Group, Department of Clinical Science, University of Bergen , Bergen , Norway"},{"name":"Department of Medicine, Haukeland University Hospital , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"2024011000445588500_CIT0001","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0140-6736(21)00136-7","article-title":"Adrenal insufficiency","volume":"397","author":"Husebye","year":"2021","journal-title":"Lancet"},{"key":"2024011000445588500_CIT0002","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1056\/NEJMra1713301","article-title":"Autoimmune polyendocrine syndromes","volume":"378","author":"Husebye","year":"2018","journal-title":"N Engl J Med"},{"key":"2024011000445588500_CIT0003","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ando.2018.03.008","article-title":"Autoimmune Addison\u2019s disease \u2013 an update on pathogenesis","volume":"79","author":"Hellesen","year":"2018","journal-title":"Ann Endocrinol"},{"key":"2024011000445588500_CIT0004","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/0140-6736(92)91829-W","article-title":"21-Hydroxylase, a major autoantigen in idiopathic Addison\u2019s disease","volume":"339","author":"Winqvist","year":"1992","journal-title":"Lancet"},{"key":"2024011000445588500_CIT0005","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1530\/EJE-20-1268","article-title":"The natural history of 21-hydroxylase autoantibodies in autoimmune Addison\u2019s disease","volume":"184","author":"Wolff","year":"2021","journal-title":"Eur J Endocrinol"},{"key":"2024011000445588500_CIT0006","doi-asserted-by":"crossref","first-page":"5117","DOI":"10.1210\/jc.2009-1115","article-title":"T cell responses to steroid cytochrome P450 21-hydroxylase in patients with autoimmune primary adrenal insufficiency","volume":"94","author":"Bratland","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2024011000445588500_CIT0007","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.4049\/jimmunol.1400056","article-title":"High frequency of cytolytic 21-hydroxylase\u2013specific CD8+ T cells in autoimmune Addison\u2019s disease patients","volume":"193","author":"Dawoodji","year":"2014","journal-title":"J Immunol"},{"key":"2024011000445588500_CIT0008","doi-asserted-by":"crossref","first-page":"742848","DOI":"10.3389\/fimmu.2021.742848","article-title":"21-Hydroxylase-specific CD8+ T cells in autoimmune Addison\u2019s disease are restricted by HLA-A2 and HLA-C7 molecules","volume":"12","author":"Hellesen","year":"2021","journal-title":"Front Immunol"},{"key":"2024011000445588500_CIT0009","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). 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