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Related Experiment Video

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Leukemia Inhibitory Factor Inhibits Plasmacytoid Dendritic Cell Function and Development.

Renata Sesti-Costa1,2, Luisa Cervantes-Barragan1, Melissa K Swiecki1

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and.

Journal of Immunology (Baltimore, Md. : 1950)
|March 15, 2020
PubMed
Summary
This summary is machine-generated.

Leukemia inhibitory factor (LIF) signaling inhibits plasmacytoid dendritic cell (pDC) function and development by inducing Id2. This pathway can be targeted to modulate type I interferon (IFN-I) production in autoimmune and viral diseases.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Plasmacytoid dendritic cells (pDCs) are crucial for producing type I interferons (IFN-I) upon viral nucleic acid detection.
  • pDC generation and maintenance are regulated by the transcription factor E2-2 and its repressor Id2.

Purpose of the Study:

  • To investigate the role of Leukemia Inhibitory Factor (LIF) receptor signaling in pDC function and development.
  • To elucidate the molecular mechanisms by which LIF influences pDC responses and differentiation.

Main Methods:

  • Analysis of LIF receptor (LIFR) expression in mouse pDCs.
  • Stimulation of pDCs with LIF and assessment of cytokine production (IFN-I, TNF, IL-6).
  • Measurement of STAT3 target gene expression (SOCS3, Bcl3, Id2).
  • Evaluation of pDC development and IFN-I responses in LIFR-deficient mice.

Main Results:

  • Mouse pDCs express LIFR, and LIF stimulation inhibits IFN-I, TNF, and IL-6 responses.
  • LIF induces STAT3 target genes SOCS3 and Bcl3, which inhibit IFN-I and NF-κB signaling.
  • LIF paradoxically induces Id2, the repressor of pDC development, and impairs pDC development from progenitors.
  • LIFR deficiency in hematopoietic cells enhances pDC development and IFN-I responses during viral infection.

Conclusions:

  • An LIF-driven STAT3 pathway induces SOCS3, Bcl3, and Id2, making pDCs and their progenitors refractory to stimuli.
  • This pathway negatively regulates pDC function and development, impacting immune responses.
  • Targeting this LIF-STAT3-Id2 axis offers potential therapeutic strategies for autoimmune diseases and viral infections.