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Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism.

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  • معلومة اضافية
    • Author-Supplied Keywords:
      Animal cells
      Biochemistry
      Biology and life sciences
      Blood cells
      Cell biology
      Cell differentiation
      Cellular types
      Cytokines
      Developmental biology
      DNA-binding proteins
      Enzymes
      Enzymology
      Gene expression
      Gene regulation
      Genetics
      Immune cells
      Immune physiology
      Immune receptors
      Immune system
      Immune system proteins
      Immunology
      Innate immune system
      Luciferase
      Medicine and health sciences
      Molecular development
      Nucleotides
      Oligonucleotides
      Oxidoreductases
      Physiology
      Proteins
      Regulatory proteins
      Research Article
      Signal transduction
      T cell receptors
      T cells
      Transcription factors
      White blood cells
    • Abstract:
      CRTh2 (encoded by PTGDR2) is a G-protein coupled receptor expressed by Th2 cells as well as eosinophils, basophils and innate lymphoid cells (ILC)2s. Activation of CRTh2, by its ligand prostaglandin (PG)D2, mediates production of type 2 cytokines (IL-4, IL-5 and IL-13), chemotaxis and inhibition of apoptosis. As such, the PGD2-CRTh2 pathway is considered important to the development and maintenance of allergic inflammation. Expression of CRTh2 is mediated by the transcription factor GATA3 during Th2 cell differentiation and within ILC2s. Other than this, relatively little is known regarding the cellular and molecular mechanisms regulating expression of CRTh2. Here, we show using primary human Th2 cells that activation (24hrs) through TCR crosslinking (αCD3/αCD28) reduced expression of both mRNA and surface levels of CRTh2 assessed by flow cytometry and qRT-PCR. This effect took more than 4 hours and expression was recovered following removal of activation. EMSA analysis revealed that GATA3 and NFAT1 can bind independently to overlapping sites within a CRTh2 promoter probe. NFAT1 over-expression resulted in loss of GATA3-mediated CRTh2 promoter activity, while inhibition of NFAT using a peptide inhibitor (VIVIT) coincided with recovery of CRTh2 expression. Collectively these data indicate that expression of CRTh2 is regulated through the competitive action of GATA3 and NFAT1. Though prolonged activation led to NFAT1-mediated downregulation, CRTh2 was re-expressed when stimulus was removed suggesting this is a dynamic mechanism and may play a role in PGD2-CRTh2 mediated allergic inflammation. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, CANADA
      2Department of Pathology and Laboratory Medicine, Western University, London, Ontario, CANADA
    • Full Text Word Count:
      11077
    • ISSN:
      1932-6203
    • Accession Number:
      10.1371/journal.pone.0199156
    • Accession Number:
      130506220
  • Citations
    • ABNT:
      MACLEAN SCOTT, E. et al. Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism. PLoS ONE, [s. l.], v. 13, n. 7, p. 1–22, 2018. DOI 10.1371/journal.pone.0199156. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=130506220&custid=s8280428. Acesso em: 15 ago. 2020.
    • AMA:
      MacLean Scott E, Solomon LA, Davidson C, Storie J, Palikhe NS, Cameron L. Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism. PLoS ONE. 2018;13(7):1-22. doi:10.1371/journal.pone.0199156
    • APA:
      MacLean Scott, E., Solomon, L. A., Davidson, C., Storie, J., Palikhe, N. S., & Cameron, L. (2018). Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism. PLoS ONE, 13(7), 1–22. https://doi.org/10.1371/journal.pone.0199156
    • Chicago/Turabian: Author-Date:
      MacLean Scott, Emily, Lauren A. Solomon, Courtney Davidson, Jessica Storie, Nami Shrestha Palikhe, and Lisa Cameron. 2018. “Activation of Th2 Cells Downregulates CRTh2 through an NFAT1 Mediated Mechanism.” PLoS ONE 13 (7): 1–22. doi:10.1371/journal.pone.0199156.
    • Harvard:
      MacLean Scott, E. et al. (2018) ‘Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism’, PLoS ONE, 13(7), pp. 1–22. doi: 10.1371/journal.pone.0199156.
    • Harvard: Australian:
      MacLean Scott, E, Solomon, LA, Davidson, C, Storie, J, Palikhe, NS & Cameron, L 2018, ‘Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism’, PLoS ONE, vol. 13, no. 7, pp. 1–22, viewed 15 August 2020, .
    • MLA:
      MacLean Scott, Emily, et al. “Activation of Th2 Cells Downregulates CRTh2 through an NFAT1 Mediated Mechanism.” PLoS ONE, vol. 13, no. 7, July 2018, pp. 1–22. EBSCOhost, doi:10.1371/journal.pone.0199156.
    • Chicago/Turabian: Humanities:
      MacLean Scott, Emily, Lauren A. Solomon, Courtney Davidson, Jessica Storie, Nami Shrestha Palikhe, and Lisa Cameron. “Activation of Th2 Cells Downregulates CRTh2 through an NFAT1 Mediated Mechanism.” PLoS ONE 13, no. 7 (July 3, 2018): 1–22. doi:10.1371/journal.pone.0199156.
    • Vancouver/ICMJE:
      MacLean Scott E, Solomon LA, Davidson C, Storie J, Palikhe NS, Cameron L. Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism. PLoS ONE [Internet]. 2018 Jul 3 [cited 2020 Aug 15];13(7):1–22. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=130506220&custid=s8280428