{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:06:16Z","timestamp":1791533176054,"version":"4.3.4"},"reference-count":55,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stress and the attendant rise in glucocorticoids (GCs) results in a potent suppression of the immune system. To date, the anti-inflammatory role of GCs, via activation of the glucocorticoid receptor, has been well-characterized. However, cortisol, the primary GC in both fish and humans, also signals through the high-affinity mineralocorticoid receptor (MR), of which the immunomodulatory role is poorly understood. Here, we tested the hypothesis that MR is a key modulator of leukocyte function during inflammation. Using transgenic MR knockout zebrafish with fluorescently labelled leukocytes, we show that a loss of MR results in a global reduction in macrophage number during key development stages. This reduction was associated with impaired macrophage proliferation and responsivity to developmental distribution signals, as well as increased susceptibility to cell death. Using a tail fin amputation in zebrafish larvae as a model for localized inflammation, we further showed that MR knockout larvae display a reduced ability to produce more macrophages under periods of inflammation (emergency myelopoiesis). Finally, we treated wild-type larvae with an MR antagonist (eplerenone) during definitive hematopoiesis, when the macrophages had differentiated normally throughout the larvae. This pharmacological blockade of MR reduced the migration of macrophages toward a wound, which was associated with reduced macrophage Ccr2 signalling. Eplerenone treatment also abolished the cortisol-induced inhibition of macrophage migration, suggesting a role for MR in cortisol-mediated anti-inflammatory action. Taken together, our work reveals that MR is a key modulator of the innate immune response to inflammation under both basal and stressed conditions.<\/jats:p>","DOI":"10.1210\/endocr\/bqad127","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T16:27:37Z","timestamp":1692289657000},"source":"Crossref","is-referenced-by-count":23,"title":["The Mineralocorticoid Receptor Plays a Crucial Role in Macrophage Development and Function"],"prefix":"10.1210","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1489-8336","authenticated-orcid":false,"given":"Erin","family":"Faught","sequence":"first","affiliation":[{"name":"Institute of Biology Leiden, Leiden University , Leiden 2333CC , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-8936","authenticated-orcid":false,"given":"Marcel J M","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Institute of Biology Leiden, Leiden University , Leiden 2333CC , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"issue":"1-2","key":"2023091318111021000_bqad127-B1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000362724","article-title":"One hormone, two actions: anti- and pro-inflammatory effects of glucocorticoids","volume":"22","author":"Cruz-Topete","year":"2014","journal-title":"Neuroimmunomodulation"},{"issue":"3","key":"2023091318111021000_bqad127-B2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1023\/A:1008924418720","article-title":"Cortisol in teleosts: dynamics, mechanisms of action, and metabolic regulation","volume":"9","author":"Mommsen","year":"1999","journal-title":"Rev Fish Biol Fish"},{"issue":"1","key":"2023091318111021000_bqad127-B3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.physiol.67.040403.120816","article-title":"Endocrinology of the stress response","volume":"67","author":"Charmandari","year":"2005","journal-title":"Annu Rev Physiol"},{"issue":"1","key":"2023091318111021000_bqad127-B4","first-page":"55","article-title":"How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions","volume":"21","author":"Sapolsky","year":"2000","journal-title":"Endocr Rev"},{"issue":"7","key":"2023091318111021000_bqad127-B5","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/cvr\/cvy092","article-title":"The mineralocorticoid receptor as a modulator of innate immunity and atherosclerosis","volume":"114","author":"van der Heijden","year":"2018","journal-title":"Cardiovasc Res"},{"key":"2023091318111021000_bqad127-B6","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.3389\/fimmu.2019.01859","article-title":"Fighting the fire: mechanisms of inflammatory gene regulation by the glucocorticoid receptor","volume":"10","author":"Escoter-torres","year":"2019","journal-title":"Front Immunol"},{"issue":"5","key":"2023091318111021000_bqad127-B7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/10253890.2018.1456526","article-title":"Mineralocorticoid and glucocorticoid 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