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Related Concept Videos

T Cell Types and Functions01:24

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Generation of Human Chimeric Antigen Receptor Regulatory T Cells
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HIF-2α is indispensable for regulatory T cell function.

Tzu-Sheng Hsu1, Yen-Lin Lin1, Yu-An Wang1

  • 1Institute of Molecular Biology, Academia Sinica, 11529, Taipei, Taiwan.

Nature Communications
|October 7, 2020
PubMed
Summary
This summary is machine-generated.

Hypoxia-inducible factor 2-alpha (HIF-2α) is crucial for regulatory T (Treg) cell function. Targeting HIF-2α in Treg cells may offer new therapeutic strategies for immune-related diseases and cancer.

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Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Biology

Background:

  • Hypoxia-inducible factors (HIFs) regulate cellular responses to low oxygen.
  • The specific roles of HIF-1α and HIF-2α in regulatory T (Treg) cells remain unclear.
  • Treg cells are critical for immune homeostasis and preventing autoimmunity.

Purpose of the Study:

  • To investigate the distinct functions of HIF-1α and HIF-2α in Treg cells.
  • To explore the therapeutic potential of targeting HIFs in Treg-mediated diseases.
  • To elucidate the regulatory relationship between HIF-1α and HIF-2α within Treg cells.

Main Methods:

  • Foxp3-specific knockout mouse models for HIF-1α and HIF-2α.
  • Assessment of Treg cell development and function in vitro and in vivo.
  • Analysis of Treg cell reprogramming into IL-17-secreting cells.
  • Evaluation of tumor growth and metastasis in KO mouse models.

Main Results:

  • Treg cell development is unaffected by HIF-1α or HIF-2α knockout.
  • HIF-2α knockout Treg cells exhibit impaired suppression of colitis and airway hypersensitivity.
  • HIF-2α knockout Treg cells show increased reprogramming to IL-17-producing cells.
  • HIF-2α represses HIF-1α expression; HIF-1α upregulation in HIF-2α KO Treg cells.
  • Loss of HIF-2α in Treg cells confers resistance to tumor growth and metastasis.

Conclusions:

  • HIF-2α, but not HIF-1α, is essential for Treg cell suppressive function.
  • Targeting HIF-2α destabilizes Treg cells, impacting immune responses.
  • HIF-2α inhibition in Treg cells presents a potential strategy for cancer therapy and immune modulation.