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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠—such as chloroplasts and mitochondria⁠—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.
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The process of converting very light nuclei into heavier nuclei is also accompanied by the conversion of mass into large amounts of energy, a process called fusion. The principal source of energy in the sun is a net fusion reaction in which four hydrogen nuclei fuse and ultimately produce one helium nucleus and two positrons.
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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
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Nuclear Receptor Nur77 Deficiency Alters Dendritic Cell Function.

Nina Tel-Karthaus1, Esther D Kers-Rebel1, Maaike W Looman1

  • 1Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Frontiers in Immunology
|August 21, 2018
PubMed
Summary

Nuclear receptor Nur77 influences dendritic cell (DC) activation. Nur77 deficiency enhances DC inflammatory responses, while its activation diminishes DC function, suggesting Nur77 as a therapeutic target for immunotherapies.

Keywords:
NR4ANur77dendritic cell-based immunotherapydendritic cellsnuclear receptors

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Dendritic cells (DCs) are crucial for immune responses.
  • Nuclear receptors (NRs) regulate immune cell function.
  • Nur77, an NR4A subfamily member, is expressed in immune cells.

Purpose of the Study:

  • To investigate the role of Nur77 in murine and human dendritic cell function.
  • To determine if Nur77 expression is essential for DC development.
  • To explore Nur77's impact on DC activation and subsequent T cell responses.

Main Methods:

  • Expression analysis of Nur77 in murine and human DCs (in vitro and ex vivo).
  • siRNA-mediated knockdown of Nur77 in human monocyte-derived DCs (moDCs).
  • Analysis of Nur77-deficient (Nur77-/-) murine DCs.
  • Assessment of DC activation and T cell proliferation/IFNγ production.

Main Results:

  • Nur77 is expressed in various DC subsets but dispensable for DC development.
  • Nur77-deficient DCs exhibit enhanced inflammatory responses and increased T cell proliferation.
  • Activation of Nur77 in human moDCs with 6-mercaptopurine reduces DC activation and impairs T cell IFNγ production.

Conclusions:

  • Nur77 plays a significant, previously unrecognized role in modulating dendritic cell activation status.
  • Targeting Nur77 offers potential for developing novel immunotherapies.
  • Nur77 modulation may be beneficial for cancer immunotherapy or treating autoimmune diseases.