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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Protein kinase C-theta mediates negative feedback on regulatory T cell function
Alexandra Zanin-Zhorov1, Yi Ding, Sudha Kumari
1Molecular Pathogenesis Program, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Science (New York, N.Y.)
|March 27, 2010
Summary
Protein kinase C-theta (PKC-theta) inhibits regulatory T cell (Treg) function. Blocking PKC-theta enhances Treg activity, offering therapeutic potential for inflammatory diseases by restoring Treg function in the presence of inflammatory cytokines.
Area of Science:
- Immunology
- Cellular Biology
- Inflammation Research
Background:
- Regulatory T cells (Tregs) control immune responses but are inhibited by tumor necrosis factor-alpha (TNF-alpha).
- Protein kinase C-theta (PKC-theta) is crucial for effector T cell (Teff) activation.
- PKC-theta's role in Treg function was previously unclear.
Purpose of the Study:
- To investigate the role of PKC-theta in Treg function and its interaction with TNF-alpha.
- To determine if inhibiting PKC-theta can restore Treg activity.
Main Methods:
- Studied PKC-theta localization at the Treg immunological synapse.
- Utilized PKC-theta blockade in in vitro and in vivo models.
- Assessed Treg function in the presence of TNF-alpha and in disease models.
Main Results:
- PKC-theta was sequestered away from the Treg immunological synapse.
- PKC-theta blockade enhanced Treg-mediated suppression.
- Inhibition of PKC-theta protected Tregs from TNF-alpha-induced inactivation.
- Restored Treg function in rheumatoid arthritis patients and improved colitis protection in mice.
Conclusions:
- PKC-theta acts as an inhibitor of Treg function.
- Targeting PKC-theta can overcome inflammatory cytokine inhibition of Tregs.
- PKC-theta inhibition represents a promising therapeutic strategy for inflammatory diseases.
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