Molecular regulation and endogenous expression of CRTh2 in in vitro differentiated CRTh2+ Th2 cells

  • Author / Creator
    MacLean, Emily Iris
  • Allergic inflammation is mediated by T helper 2 (Th2) cells. Chemoattractant receptor homologous molecule expressed on Th2 cells (CRTh2) is expressed by Th2 cells and mediates chemotaxis and production of the Th2 cytokines interleukin (IL)-4, IL-5 and IL-13. To understand the molecular regulation of CRTh2, we studied the promoter and found putative binding sites for GATA3 and nuclear factor in activated T cells (NFAT), transcription factors known to regulate Th2 cytokine expression. We hypothesized these factors also regulate transcription of CRTh2. Using a reporter construct with the proximal region of the CRTh2 promoter, we found transcription of CRTh2 was increased following stimulation in CRTh2+ Th2 cells. Endogenous CRTh2 was decreased following stimulation. Further, over-expression of NFAT1 decreased a GATA3 dependent increase in CRTh2 promoter activity. The discrepancy between CRTh2 endogenous expression and proximal promoter activity indicates longer regions of the CRTh2 5’ regulatory region may be important for regulation.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Medicine
  • Supervisor / co-supervisor and their department(s)
    • Vliagoftis, Harissios (Medicine)
    • Cameron, Lisa (Medicine)
  • Examining committee members and their departments
    • Baldwin, Troy (Medical Microbiology and Immunology)
    • Burshtyn, Deborah (Medical Microbiology and Immunology)