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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Immunostimulatory RNA blocks suppression by regulatory T cells
David Anz1, Viktor H Koelzer, Stefan Moder
1Division of Clinical Pharmacology, Center of Integrated Protein Science Munich, University of Munich, Munich, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|December 8, 2009
Summary
Viral RNA inhibits regulatory T (Treg) cell function by activating specific helicases like RIG-I and MDA-5. This mechanism is crucial for mounting an effective antiviral immune response during infection.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Regulatory T (Treg) cells are vital for immune homeostasis through immune suppression.
- Mechanisms inhibiting Treg cell function during viral infections remain largely unknown.
- Viral RNA is a key activator of antiviral immunity.
Purpose of the Study:
- To investigate the impact of immunostimulatory RNA and RNA viruses on Treg cell function.
- To elucidate the specific molecular pathways involved in Treg cell inhibition during viral infections.
Main Methods:
- Treatment of Treg cells with synthetic RNA oligonucleotides and RNA viruses (EMCV, Sendai virus).
- Assessment of Treg cell suppressive function and dependence on Toll-like receptor 7 (TLR7) and interleukin-6 (IL-6).
- Analysis of RIG-I-like helicase (RIG-I, MDA-5) expression and function in Treg cells and T effector cells.
- Utilized MDA-5-deficient mice to confirm the role of MDA-5 in Treg cell dysfunction during viral infection.
Main Results:
- Synthetic RNA oligonucleotides inhibit Treg cell suppression in a sequence-dependent manner, mediated by TLR7 activation of antigen-presenting cells (APCs) and IL-6 production.
- RNA viruses (EMCV, Sendai virus) also block Treg cell function, dependent on RIG-I and MDA-5 activation.
- This inhibition occurs even without APCs, as Treg cells themselves express RIG-I and MDA-5.
- Loss of Treg cell function during EMCV infection is critically dependent on MDA-5 expression within Treg cells.
Conclusions:
- Activation of RIG-I-like helicases (RIG-I, MDA-5) on Treg cells directly inhibits their suppressive function.
- This represents a novel mechanism by which the immune system overcomes Treg-mediated suppression to establish antiviral immunity.
- Understanding this pathway offers potential therapeutic targets for modulating immune responses during viral infections.
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