> Detailanzeige

Banerjee, Daliya; Zhao, Linlin; Wu, Lan; Palanichamy, Arumugam; Ergun, Ayla; Peng, Liaomin; Quigley, Catherine; Hamann, Stefan; Dunstan, Robert; Cullen, Patrick; Allaire, Norm; Guertin, Kevin; Wang, Tao; Chao, Jianhua; Loh, Christine; Fontenot, Jason D.

Small molecule mediated inhibition of RORγ‐dependent gene expression and autoimmune disease pathology in vivo

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Small molecule mediated inhibition of RORγ‐dependent gene expression and autoimmune disease pathology in vivo
  • Beteiligte: Banerjee, Daliya; Zhao, Linlin; Wu, Lan; Palanichamy, Arumugam; Ergun, Ayla; Peng, Liaomin; Quigley, Catherine; Hamann, Stefan; Dunstan, Robert; Cullen, Patrick; Allaire, Norm; Guertin, Kevin; Wang, Tao; Chao, Jianhua; Loh, Christine; Fontenot, Jason D.
  • Erschienen: Wiley, 2016
  • Erschienen in: Immunology, 147 (2016) 4, Seite 399-413
  • Sprache: Englisch
  • DOI: 10.1111/imm.12570
  • ISSN: 0019-2805; 1365-2567
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Summary</jats:title><jats:p>Retinoic acid receptor‐related orphan nuclear receptor <jats:italic>γ</jats:italic> (<jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic>) orchestrates a pro‐inflammatory gene expression programme in multiple lymphocyte lineages including T helper type 17 (Th17) cells, <jats:italic>γδ</jats:italic> T cells, innate lymphoid cells and lymphoid tissue inducer cells. There is compelling evidence that <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic>‐expressing cells are relevant targets for therapeutic intervention in the treatment of autoimmune and inflammatory diseases. Unlike Th17 cells, where <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic> expression is induced under specific pro‐inflammatory conditions, <jats:italic>γδ</jats:italic> T cells and other innate‐like immune cells express <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic> in the steady state. Small molecule mediated disruption of <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic> function in cells with pre‐existing <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic> transcriptional complexes represents a significant and challenging pharmacological hurdle. We present data demonstrating that a novel, selective and potent small molecule <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic> inhibitor can block the <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic>‐dependent gene expression programme in both Th17 cells and <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic>‐expressing <jats:italic>γδ</jats:italic> T cells as well as a disease‐relevant subset of human <jats:styled-content style="fixed-case">ROR</jats:styled-content><jats:italic>γ</jats:italic>‐expressing memory T cells. Importantly, systemic administration of this inhibitor <jats:italic>in vivo</jats:italic> limits pathology in an innate lymphocyte‐driven mouse model of psoriasis.</jats:p>
  • Zugangsstatus: Freier Zugang