{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:32:06Z","timestamp":1787873526053,"version":"build-2784847793"},"posted":{"date-parts":[[2025,4,9]]},"group-title":"Immunology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    We recently identified a molecular mechanism involving beta-adrenergic 1 and 2 receptors (\u03b21\/2) in the development of T\n                    <jats:sub>H<\/jats:sub>\n                    17 lymphocytes. Pharmacological and genetic inhibition of these receptors in combination, but not separately, impaired the ability of T-lymphocytes to produce proinflammatory interleukin 17A (IL-17A) and instead promoted the production of protective T\n                    <jats:sub>reg<\/jats:sub>\n                    cells that secrete anti-inflammatory interleukin-10 (IL-10). However, it remained unclear whether this regulatory mechanism could serve as a novel therapeutic approach for autoimmune disorders mediated by IL-17A-producing T-lymphocytes.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS) characterized by an autoimmune response where both T-lymphocytes and IL-17A are implicated in the pathogenesis of the disease. Using an animal model of MS, termed experimental autoimmune encephalomyelitis (EAE), we addressed the impact of beta adrenergic receptor blockade (genetically and pharmacologically) on EAE disease progression, severity, and T\n                    <jats:sub>H<\/jats:sub>\n                    17\/T\n                    <jats:sub>reg<\/jats:sub>\n                    balance.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The genetic deletion \u03b21\/2 receptors, either systemically or specifically in T-lymphocytes, significantly attenuated EAE disease severity and animal weight loss. Pharmacological blockade of \u03b21\/2 receptors with either propranolol (lipophilic) or nadolol (aqueous) limited disease severity and weight loss similar to the genetic models. All models showed degrees of shifted T\n                    <jats:sub>H<\/jats:sub>\n                    17\/T\n                    <jats:sub>reg<\/jats:sub>\n                    balance (suppressing T\n                    <jats:sub>H<\/jats:sub>\n                    17 and promoting T\n                    <jats:sub>reg<\/jats:sub>\n                    ) and decreased T-lymphocyte IL-17A production. Importantly, pharmacological blockade was initiated at the time of symptom development, which mimics the typical time where diagnosis of disease would occur.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Our data depict a novel role for \u03b21\/2 adrenergic signaling in the control of T\n                    <jats:sub>H<\/jats:sub>\n                    17\/T\n                    <jats:sub>reg<\/jats:sub>\n                    cells in EAE. These findings provide new insight into the disease progression as well as provide a potential new pharmacological therapy for IL-17A-related autoimmune diseases.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.05.647384","type":"posted-content","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T21:40:11Z","timestamp":1744234811000},"source":"Crossref","is-referenced-by-count":3,"title":["Beta Adrenergic Signaling as a Therapeutic Target for Autoimmunity"],"prefix":"10.64898","author":[{"given":"Tatlock H.","family":"Lauten","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Natour","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren J.","family":"Pitts","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline N.","family":"Jojo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke L.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-1428","authenticated-orcid":false,"given":"Adam J.","family":"Case","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States"},{"name":"Department of Medical Physiology, Texas A&M University, Bryan, TX, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041203431692000_2025.04.05.647384v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104293"},{"key":"2026041203431692000_2025.04.05.647384v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.03.008"},{"key":"2026041203431692000_2025.04.05.647384v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(84)90230-2"},{"key":"2026041203431692000_2025.04.05.647384v1.4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.135.2.755"},{"key":"2026041203431692000_2025.04.05.647384v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410080509"},{"key":"2026041203431692000_2025.04.05.647384v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature01321"},{"key":"2026041203431692000_2025.04.05.647384v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.189"},{"key":"2026041203431692000_2025.04.05.647384v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2013.12.007"},{"key":"2026041203431692000_2025.04.05.647384v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209985"},{"key":"2026041203431692000_2025.04.05.647384v1.10","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00405"},{"key":"2026041203431692000_2025.04.05.647384v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"2026041203431692000_2025.04.05.647384v1.12","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.268573"},{"key":"2026041203431692000_2025.04.05.647384v1.13","doi-asserted-by":"publisher","DOI":"10.1113\/EP085559"},{"key":"2026041203431692000_2025.04.05.647384v1.14","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1125492"},{"key":"2026041203431692000_2025.04.05.647384v1.15","first-page":"1061","article-title":"T H 17\/Treg lymphocyte balance is regulated by beta adrenergic and cAMP signaling","volume":"123","year":"2024","journal-title":"Brain Behav Immun"},{"key":"2026041203431692000_2025.04.05.647384v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.10.010"},{"key":"2026041203431692000_2025.04.05.647384v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.044"},{"key":"2026041203431692000_2025.04.05.647384v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.021"},{"key":"2026041203431692000_2025.04.05.647384v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00746-9"},{"key":"2026041203431692000_2025.04.05.647384v1.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01302.x"},{"key":"2026041203431692000_2025.04.05.647384v1.21","doi-asserted-by":"crossref","unstructured":"Hiltensperger M , and Korn T . The Interleukin (IL)-23\/T helper (Th)17 Axis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018;8(1).","DOI":"10.1101\/cshperspect.a029637"},{"key":"2026041203431692000_2025.04.05.647384v1.22","doi-asserted-by":"publisher","DOI":"10.2174\/1389450117666160307144027"},{"key":"2026041203431692000_2025.04.05.647384v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2018.09.001"},{"key":"2026041203431692000_2025.04.05.647384v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsgos.2022.12.002"},{"key":"2026041203431692000_2025.04.05.647384v1.25","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01246-z"},{"key":"2026041203431692000_2025.04.05.647384v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.05.007"},{"key":"2026041203431692000_2025.04.05.647384v1.27","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1105625"},{"key":"2026041203431692000_2025.04.05.647384v1.28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164609"},{"key":"2026041203431692000_2025.04.05.647384v1.29","doi-asserted-by":"publisher","DOI":"10.1159\/000360579"},{"key":"2026041203431692000_2025.04.05.647384v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.08.001"},{"key":"2026041203431692000_2025.04.05.647384v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.01.003"},{"key":"2026041203431692000_2025.04.05.647384v1.32","doi-asserted-by":"publisher","DOI":"10.1006\/brbi.2001.0639"},{"issue":"4","key":"2026041203431692000_2025.04.05.647384v1.33","first-page":"544","article-title":"Inhibition of lymphocyte activation by catecholamines: evidence for a non-classical mechanism of catecholamine action","volume":"85","year":"1995","journal-title":"Immunology"},{"key":"2026041203431692000_2025.04.05.647384v1.34","doi-asserted-by":"publisher","DOI":"10.1159\/000129670"},{"key":"2026041203431692000_2025.04.05.647384v1.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05427.x"},{"key":"2026041203431692000_2025.04.05.647384v1.36","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-019-09852-3"},{"key":"2026041203431692000_2025.04.05.647384v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2011.02.004"},{"key":"2026041203431692000_2025.04.05.647384v1.38","doi-asserted-by":"publisher","DOI":"10.2174\/187152410790780154"},{"key":"2026041203431692000_2025.04.05.647384v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(88)90125-7"},{"key":"2026041203431692000_2025.04.05.647384v1.40","doi-asserted-by":"publisher","DOI":"10.1006\/brbi.1999.0549"},{"key":"2026041203431692000_2025.04.05.647384v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2016.08.006"},{"key":"2026041203431692000_2025.04.05.647384v1.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182416"},{"key":"2026041203431692000_2025.04.05.647384v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(89)90138-0"},{"key":"2026041203431692000_2025.04.05.647384v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104665"},{"key":"2026041203431692000_2025.04.05.647384v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-015-0405-3"},{"key":"2026041203431692000_2025.04.05.647384v1.46","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140540"},{"key":"2026041203431692000_2025.04.05.647384v1.47","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.216"},{"key":"2026041203431692000_2025.04.05.647384v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-5996-y"},{"key":"2026041203431692000_2025.04.05.647384v1.49","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314258"},{"key":"2026041203431692000_2025.04.05.647384v1.50","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201601"},{"key":"2026041203431692000_2025.04.05.647384v1.51","first-page":"320","article-title":"IL-17 neutralization by subcutaneous CJM112, a fully human anti IL-17A monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis: study design of a phase 2 trial","volume":"21","year":"2015","journal-title":"Multiple Sclerosis Journal"},{"key":"2026041203431692000_2025.04.05.647384v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2007.07.002"},{"key":"2026041203431692000_2025.04.05.647384v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.110039"},{"key":"2026041203431692000_2025.04.05.647384v1.54","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0065"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.04.05.647384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T10:43:24Z","timestamp":1775990604000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.04.05.647384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":54,"URL":"https:\/\/doi.org\/10.1101\/2025.04.05.647384","relation":{},"subject":[],"published":{"date-parts":[[2025,4,9]]},"subtype":"preprint"}}