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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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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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Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Wnt activation promotes memory T cell polyfunctionality via epigenetic regulator PRMT1.

Bo-Yi Sung1,2,3,4, Yi-Hsin Lin4,5, Qiongman Kong1

  • 1Institute of Cell Engineering and.

The Journal of Clinical Investigation
|January 18, 2022
PubMed
Summary
This summary is machine-generated.

Wnt agonists promote polyfunctional T cells via epigenetic regulation by PRMT1, enhancing immunity against infections and cancer. This discovery offers a new target for T cell immunotherapy.

Keywords:
Adaptive immunityEpigeneticsImmunologyT cells

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Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • T cell polyfunctionality is crucial for immunity but its regulation is poorly understood.
  • Canonical Wnt agonists were investigated for their role in T cell responses.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying T cell polyfunctionality.
  • To investigate the role of Wnt signaling and PRMT1 in T cell function.

Main Methods:

  • Human memory CD8+ T cells were treated with Wnt agonists.
  • Gene expression, epigenetic modifications (H4R3me2a), and cytokine production (IL-2) were analyzed.
  • In vivo studies and analysis of patient samples (CMV D+/R- lung transplant) were performed.

Main Results:

  • Wnt agonists promoted polyfunctional CD8+ T cells with persistent effects, suggesting epigenetic regulation.
  • Wnt activation upregulated PRMT1, an epigenetic regulator, which was essential for enhanced polyfunctionality and IL-2 production.
  • PRMT1 mediated increased H4R3me2a at the IL-2 promoter, boosting T cell function in vitro and in vivo.
  • Wnt activation enhanced CMV-specific T cell polyfunctionality in lung transplant patient samples.

Conclusions:

  • Wnt signaling epigenetically regulates T cell polyfunctionality through PRMT1.
  • PRMT1 is a key mediator of enhanced T cell responses and a potential therapeutic target for immunotherapy.