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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 is dispensable for suppression mediated by CD25+CD4+ regulatory T cells
Kerstin Siegmund1, Nikolaus Thuille1, Katarzyna Wachowicz1
1Department for Pharmacology and Genetics, Medical University Innsbruck, Innsbruck, Austria.
Abstract:
The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay. Furthermore, in vitro-differentiated wild-type and PKCθ-deficient iTreg cells showed comparable Foxp3 expression as well as suppressive activity. However, we observed a reduced percentage of Foxp3+CD25+ CD4+ T cells in the lymphatic organs of PKCθ-deficient mice. Taken together, our results suggest that while PKCθ is involved in Treg cell differentiation in vivo, it is dispensable for Treg-mediated suppression.
Insights
Protein kinase C theta (PKCθ) is crucial for conventional T cells but not regulatory T (Treg) cell suppression. While PKCθ influences Treg cell differentiation in vivo, it is not required for their suppressive function.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Protein kinase C theta (PKCθ) is essential for conventional T cell activation.
- The role of PKCθ in regulatory T (Treg) cell function remains unclear.
Purpose of the Study:
- To investigate the role of PKCθ in Treg cell function and differentiation.
- To determine if PKCθ is required for Treg-mediated suppression.
Main Methods:
- Utilized siRNA and a selective pharmacological inhibitor (AEB071) to assess PKCθ function.
- Examined Treg cell suppressive activity in vitro using PKCθ-deficient and wild-type mice.
- Analyzed Foxp3 expression and cell percentages in lymphatic organs.
Main Results:
- Murine Treg-mediated suppression in vitro was independent of PKCθ.
- Treg cells from PKCθ-deficient mice exhibited normal suppressive activity in vitro.
- A reduced percentage of Foxp3+CD25+CD4+ T cells was observed in lymphatic organs of PKCθ-deficient mice, suggesting a role in Treg differentiation in vivo.
Conclusions:
- PKCθ is dispensable for Treg-mediated suppression.
- PKCθ plays a role in the in vivo differentiation of Treg cells.
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