{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T07:02:07Z","timestamp":1773471727194,"version":"3.50.1"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Multiple genetic associations suggest a causative relationship between Th17-related genes coding for proteins, such as IL-17A, IL-23 and STAT3, and psoriasis. Further support for this link comes from the findings that neutralizing antibodies directed against IL-17A, IL-17RA and IL-23 are efficacious in diseases like psoriasis, psoriatic arthritis and ankylosing spondylitis. ROR\u03b3t is a centrally positioned transcription factor driving Th17 polarization and cytokine secretion and modulation of ROR\u03b3t may thus provide additional benefit to patients. However, ROR\u03b3t also plays a role in the normal development of T cells in the thymus and genetic disruption of ROR\u03b3t in the mouse leads to the development of lymphoma originating in the thymus. Whilst it is not established that down-regulation of ROR\u03b3t activity would lead to the same consequence in humans, further understanding of the thymus effects is desirable to support progress of this target as a potential treatment of Th17-driven disease. Herein we present the characterisation of recently disclosed ROR\u03b3t inverse agonists demonstrating target engagement and efficacy <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> against Th17 endpoints but requiring higher concentrations <jats:italic>in vitro<\/jats:italic> to affect thymocyte apoptosis.<\/jats:p>","DOI":"10.1371\/journal.pone.0317090","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:48:39Z","timestamp":1737053319000},"page":"e0317090","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["ROR\u03b3t inverse agonists demonstrating a margin between inhibition of IL-17A and thymocyte 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