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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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According to Charles Cooley, we base our image on what we think other people see (Cooley 1902). We imagine how we must appear to others, then react to this speculation. We don certain clothes, prepare our hair in a particular manner, wear makeup, use cologne, and the like—all with the notion that our presentation of ourselves is going to affect how others perceive us. We expect a certain reaction, and, if lucky, we get the one we desire and feel good about it. But more than that, Cooley...
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Regulatory T cells sense effector T-cell activation through synchronized JunB expression.

Jingxia Wu1, Sicong Ma1,2, Agnes Hotz-Wagenblatt3

  • 1T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Heidelberg, Germany.

FEBS Letters
|April 25, 2019
PubMed
Summary

Regulatory T cells (Tregs) use the JunB transcription factor to detect effector T-cell (Teff) activation, preventing autoimmune disease and enhancing anti-tumor immunity.

Keywords:
JunBTregsantitumor T cellsautoimmunityeffector T cells

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Immune tolerance requires regulatory T cells (Tregs) to control effector T-cell (Teff) responses.
  • The mechanisms by which Tregs sense real-time Teff activation are not fully understood.

Purpose of the Study:

  • To investigate the role of the AP-1 transcription factor JunB in Treg function.
  • To elucidate how JunB in Tregs contributes to immune regulation and homeostasis.

Main Methods:

  • Investigated JunB induction in Tregs upon T-cell receptor (TCR) stimulation.
  • Utilized Treg-specific Junb deletion mouse models.
  • Analyzed inflammatory cytokine production and spontaneous inflammation.
  • Evaluated anti-tumor Teff responses in a melanoma mouse model.

Main Results:

  • JunB is induced in Tregs by TCR stimuli, mirroring its induction in Teffs.
  • Treg-specific deletion of Junb disrupts Treg identity and promotes uncontrolled Teff cytokine production.
  • Loss of Junb in Tregs leads to T-bet-dependent spontaneous inflammation.
  • JunB deficiency in Tregs enhances Teff-mediated anti-tumor responses in melanoma.

Conclusions:

  • JunB acts as a critical sensor for Tregs to detect Teff activation.
  • JunB synchronizes immune regulation with immune reactions in autoimmunity and cancer.
  • Targeting JunB in Tregs may offer therapeutic strategies for inflammatory diseases and cancer immunotherapy.