{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:56:48Z","timestamp":1768510608811,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,9]]},"group-title":"Immunology","reference-count":72,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that also presents with neuroimmune irregularities. Patients display elevated sympathetic tone and are at an increased risk of developing secondary autoimmune diseases. Previously, using a preclinical model of PTSD, we demonstrated that elimination of sympathetic signaling to T-lymphocytes specifically limited their ability to produce pro-inflammatory interleukin 17A (IL-17A); a cytokine implicated in the development of many autoimmune disorders. However, the mechanism linking sympathetic signaling to T-lymphocyte IL-17A production remained unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using a modified version of repeated social defeat stress (RSDS) that allows for both males and females, we assessed the impact of adrenergic receptor blockade (genetically and pharmacologically) and catecholamine depletion on T-lymphocyte IL-17A generation. Additionally, we explored the impact of adrenergic signaling and T-lymphocyte-produced catecholamines on both CD4+ and CD8+ T-lymphocytes polarized to IL-17A-producing phenotypes ex vivo.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Only pharmacological inhibition of the beta 1 and 2 adrenergic receptors (\u03b21\/2) significantly decreased circulating IL-17A levels after RSDS, but did not impact other pro-inflammatory cytokines (e.g., IL-6, TNF-\u03b1, and IL-10). This finding was confirmed using RSDS with both global \u03b21\/2 receptor knock-out mice, as well as by adoptively transferring \u03b21\/2 knock-out T-lymphocytes into immunodeficient hosts. Furthermore, ex vivo polarized T-lymphocytes produced significantly less IL-17A with the blockade of \u03b21\/2 signaling, even in the absence of exogenous sympathetic neurotransmitter supplementation, which suggested T-lymphocyte-produced catecholamines may be involved in IL-17A production. Indeed, pharmacological depletion of catecholamines both in vivo and ex vivo abrogated T-lymphocyte IL-17A production demonstrating the importance of immune-generated neurotransmission in pro-inflammatory cytokine generation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data depict a novel role for \u03b21\/2 adrenergic receptors and autologous catecholamine signaling during T-lymphocyte IL-17A production. These findings provide a new target for pharmacological therapy in both psychiatric and autoimmune diseases associated with IL-17A-related pathology.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.06.05.597633","type":"posted-content","created":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T17:10:10Z","timestamp":1717953010000},"source":"Crossref","is-referenced-by-count":2,"title":["Beta-adrenergic signaling and T-lymphocyte-produced catecholamines are necessary for interleukin 17A synthesis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9325-7213","authenticated-orcid":false,"given":"Tatlock H.","family":"Lauten","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3946-8658","authenticated-orcid":false,"given":"Safwan K.","family":"Elkhatib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1084-464X","authenticated-orcid":false,"given":"Tamara","family":"Natour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-5111","authenticated-orcid":false,"given":"Emily C.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline N.","family":"Jojo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-1428","authenticated-orcid":false,"given":"Adam J.","family":"Case","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024061300151168000_2024.06.05.597633v1.1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.jad.2013.08.032","article-title":"Possible involvement of oxido-nitrosative stress induced neuro-inflammatory cascade and monoaminergic pathway: underpinning the correlation between nociceptive and depressive behaviour in a rodent model","volume":"151","year":"2013","journal-title":"J Affect Disord"},{"key":"2024061300151168000_2024.06.05.597633v1.2","doi-asserted-by":"crossref","unstructured":"Baranski, G.M. , Pasupuleti, L.V. , Sifri, Z.C. , Cook, K.M. , Alzate, W.D. , Rameshwar, P. , Livingston, D.H. , Mohr, A.M ., 2013. 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