{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T19:14:07Z","timestamp":1771355647050,"version":"3.50.1"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Estrogen, a steroid hormone synthesized by both gonadal and nongonadal tissues, plays a pivotal role in modulating immune responses, including reducing relapse rates in relapsing\u2013remitting multiple sclerosis (MS). This study explored the expression of aromatase, the enzyme responsible for estrogen synthesis, in lymph nodes (LNs) and its potential role in the pathogenesis of MS using a mouse model. We utilized Cyp19-RFP mice where cells that express or have previously expressed the Cyp19 gene (encoding aromatase) are marked by red fluorescent protein (RFP). RFP was detected in the high endothelial venules of all morphologically identifiable LNs, indicating aromatase activity within these tissues. We discovered that LNs actively synthesize 17\u03b2-estradiol, but this activity declines with age. Targeted delivery of an aromatase inhibitor specifically to LNs induced an interferon-\u03b2-resistant experimental autoimmune encephalomyelitis (EAE) phenotype. This phenotype was accompanied by significant gray matter atrophy in the spinal cord. These findings underscore LNs as crucial sites of de novo 17\u03b2-estradiol production, potentially contributing to nonremitting EAE phenotypes. The observed decline in 17\u03b2-estradiol likely exacerbates MS pathogenesis in aging mice. Importantly, aromatase expression in human cervical LNs suggests that these sites may similarly contribute to estrogen synthesis in humans, potentially opening new avenues for understanding and treating MS.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgaf010","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T02:35:28Z","timestamp":1737340528000},"source":"Crossref","is-referenced-by-count":0,"title":["Decreased lymph node estrogen levels cause nonremitting progressive experimental autoimmune encephalomyelitis disease"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-7511","authenticated-orcid":false,"given":"Shehata","family":"Anwar","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences, The University of Illinois at Urbana-Champaign , 2001 South Lincoln Avenue, Urbana, IL 61802 ,","place":["USA"]},{"name":"Faculty of Veterinary Medicine, Department of Pathology, Beni-Suef University (BSU) , Beni-Suef 62511 ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Ching Patrick","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, The University of Illinois at Urbana-Champaign , 2001 South Lincoln Avenue, Urbana, IL 61802 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lazaro","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, University of Illinois at Urbana-Champaign , 1304 West Green Street, Urbana, IL 61801 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-7862","authenticated-orcid":false,"given":"Kazuhiro","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Akita University Graduate School of Medicine , 1-1-1 Hondo, Akita 010-8543 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-2935","authenticated-orcid":false,"given":"Zhengzhong","family":"Tan","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, University of Illinois at Urbana-Champaign , 1304 West Green Street, Urbana, IL 61801 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-3712","authenticated-orcid":false,"given":"Ziyuan","family":"Song","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, University of Illinois at Urbana-Champaign , 1304 West Green Street, Urbana, IL 61801 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Akita University Graduate School of Medicine , 1-1-1 Hondo, Akita 010-8543 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Minamiya","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Akita University Graduate School of Medicine , 1-1-1 Hondo, Akita 010-8543 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2561-9291","authenticated-orcid":false,"given":"Jianjun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, University of Illinois at Urbana-Champaign , 1304 West Green Street, Urbana, IL 61801 ,","place":["USA"]},{"name":"School of Engineering, Westlake University , Hangzhou 310030 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-3731","authenticated-orcid":false,"given":"CheMyong","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, The University of Illinois at Urbana-Champaign , 2001 South Lincoln Avenue, Urbana, IL 61802 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-3806","authenticated-orcid":false,"given":"Makoto","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, The University of Illinois at Urbana-Champaign , 2001 South Lincoln Avenue, Urbana, IL 61802 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"2026021713271474300_pgaf010-B1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1212\/WNL.0000000000007044","article-title":"A new way to estimate neurologic disease prevalence in the United States: illustrated with 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