TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000316386
  • Gene Name:ICOS
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:ICOS signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00470
  • Drug Name:Dronabinol
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:immune-related diseases
  • Tissue:T cell line (EL4.IL-2)

Other information

  • Title:Suppression of T cell costimulator ICOS by Delta9-tetrahydrocannabinol.
  • Journal:J Leukoc Biol
  • Published:2009
  • PubMed ID:18988696
  • Abstract:Inducible costimulator (ICOS), a prototypic T cell costimulator, is induced on activated T cells. ICOS regulates T cell activation and Th cell differentiation and is principally involved in humoral immune responses. Previous work showed that T cell accessory function is modulated by the plant-derived cannabinoid, delta-9-tetrahydrocannabinol (Delta(9)-THC). In light of an emerging role by ICOS in T cell-mediated immunity, the objective of this study was to investigate the effect of Delta(9)-THC on ICOS in activated mouse T cells. Induction of ICOS mRNA levels by phorbol ester (PMA) plus ionomycin (Io) activation in mouse splenocytes was attenuated by Delta(9)-THC in a concentration-related manner. Similar results were obtained in the mouse T cell line, EL4.IL-2. Anti-CD3/CD28 induced ICOS expression on CD4(+) splenic T cells, which was suppressed by Delta(9)-THC in a time- and concentration-related manner. The PMA/Io-induced icos promoter luciferase reporter activity was also down-regulated by Delta(9)-THC, suggesting that the suppression of ICOS expression by Delta(9)-THC occurs at the transcriptional level. Moreover, transcriptional activation of the NFAT was also down-regulated by Delta(9)-THC as shown by a NFAT luciferase reporter assay, which is consistent with a putative role of NFAT in regulating ICOS expression. Collectively, Delta(9)-THC suppresses ICOS expression in activated T cells, and this suppression may be related, in part, to its modulation of NFAT signaling. The emerging role of ICOS in a wide range of immune-related diseases also suggests that it may represent a potential therapeutic target, which could be modulated by cannabinoid compounds.
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