{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:58:51Z","timestamp":1785243531104,"version":"3.55.0"},"reference-count":226,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH research","award":["AI146252"],"award-info":[{"award-number":["AI146252"]}]},{"name":"NIH research","award":["AG073720"],"award-info":[{"award-number":["AG073720"]}]},{"name":"NIH research","award":["P01-AG051428"],"award-info":[{"award-number":["P01-AG051428"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Psychological stress arises when individuals perceive demands as exceeding their capacity to cope. Social stress can be acute, such as giving a presentation, producing transient increases in heart rate, blood pressure, and neuroendocrine activation, or chronic, in which stressors persist over extended periods. Chronic psychosocial stress disrupts immune homeostasis and contributes to anxiety, depression, and post-traumatic stress, while also increasing risk for infections, inflammatory and autoimmune diseases, cardiovascular disease, metabolic dysfunction, and cancer. Persistent stress engages interconnected neuroendocrine\u2013immune networks, including the hypothalamic\u2013pituitary\u2013adrenal axis, the sympathetic\u2013adrenomedullary system, and the gut microbiota\u2013brain\u2013immune axis, leading to sustained glucocorticoid and catecholamine signaling, gut dysbiosis, impaired barrier integrity, and altered microbial metabolite profiles. In this review, we summarize the molecular and cellular mechanisms by which these axes remodel innate and adaptive immunity and shape disease susceptibility. Using social defeat and social isolation in mice as model systems, we highlight how chronic social stress reprograms immune responses in key tissues, including the lung, brain, and gut.<\/jats:p>","DOI":"10.3390\/cells15151356","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:45:26Z","timestamp":1785239126000},"page":"1356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Social Stress and Immune Dysregulation: Integrating Neuroendocrine Signaling, Microbiota, and Tissue-Specific Responses"],"prefix":"10.3390","volume":"15","author":[{"given":"William P.","family":"Lafuse","sequence":"first","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murugesan V. S.","family":"Rajaram","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.6267699","article-title":"Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin","volume":"213","author":"Vale","year":"1981","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Burford, N.G., Webster, N.A., and Cruz-Topete, D. (2017). Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System. Int. J. Mol. 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