{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:22:20Z","timestamp":1768407740026,"version":"3.49.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Arnica montana<\/jats:italic>\n                    L. (Arnica) has a long history of use in treating inflammation and soft tissue injury, yet its immunomodulatory mechanisms remain largely unexplored. In this study, we investigated the effects of distinct Arnica extracts\u00a0- derived from different plant parts (root or whole plant) and manufacturing processes - on primary human T cells. We also compared their effects with those of the pure compounds helenalin and thymol. All extracts inhibited T cell activation and proliferation. This could be traced back to reduced IL-2 responsiveness due to decreased CD25 (IL\u20132R\u03b1 chain) expression, accompanied by reduced IL-2 production. Transcriptomic analysis (nCounter) and gene set enrichment revealed that the extracts target key T cell receptor (TCR) signaling pathways. Mechanistically, the hydroethanolic root extract selectively inhibited NF\u03baB DNA binding, while the aqueous fermented extract predominantly suppressed NFAT-dependent gene expression. The hydroethanolic whole plant extract exerted a moderate effect on both pathways. These findings identify Arnica extracts as promising modulators of human TCR signaling and support their potential in regulating T cell-driven inflammatory responses, with implications for muscle healing and chronic inflammatory diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1655212","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T05:43:20Z","timestamp":1760507000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Distinct Arnica montana L. extracts modulate human T cell activation in different ways via differential inhibition of NF\u03baB and NFAT pathways"],"prefix":"10.3389","volume":"16","author":[{"given":"Karina M.","family":"Berschneider","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Wetterauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Sticht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Orlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Jahraus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning","family":"Kirchgessner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia","family":"Zuieva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"W\u00f6lfl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Lairikyengbam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Verena","family":"Beier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Wabnitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pille","family":"Wetterauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schmiech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Samstag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12724","article-title":"Arnica montana L. - a plant of healing: review","volume":"69","author":"Kriplani","year":"2017","journal-title":"J Pharm Pharmacol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-32067","article-title":"Studies on the anti-inflammatory activity of phytopharmaceuticals prepared from Arnica flowers","volume":"68","author":"Klaas","year":"2002","journal-title":"Planta Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.07.004","article-title":"Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms","volume":"46","author":"Berges","year":"2009","journal-title":"Mol Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2174\/1389450119666181012125230","article-title":"Helenalin - a sesquiterpene lactone with multidirectional activity","volume":"20","author":"Drogosz","year":"2019","journal-title":"Curr Drug Targets."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33508","article-title":"The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65","volume":"273","author":"Lyss","year":"1998","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28114379","article-title":"Localization of sesquiterpene lactones biosynthesis in flowers of arnica taxa","volume":"28","author":"Parafiniuk","year":"2023","journal-title":"Molecules"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-969856","article-title":"Helenalin- and 11,13-Dihydrohelenalinester from Flowers of Arnica montana","volume":"49","author":"Willuhn","year":"1983","journal-title":"]. 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