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Updated: Jun 18, 2026
08:02
In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
DC expressing transgene Foxp3 are regulatory APC
Michael W Lipscomb1, Jennifer L Taylor, Cristina J Goldbach
1Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
European Journal of Immunology
|November 27, 2009
Summary
Engineered dendritic cells (DCs) expressing Foxp3 suppress T-cell proliferation and type-1 immunity. These regulatory DCs promote type-2 and regulatory T-cell (Treg) responses, offering potential for treating autoimmunity and transplant rejection.
Area of Science:
- Immunology
- Cell Biology
- Transplantation Science
Background:
- Tolerogenic dendritic cells (DCs) and Foxp3(+) regulatory T cells (Tregs) are crucial for immune tolerance.
- Dysregulation of these cells contributes to autoimmunity and allograft rejection.
Purpose of the Study:
- To investigate the immunomodulatory effects of ectopically expressing Foxp3 in human DCs (DC.Foxp3).
- To assess the potential of DC.Foxp3 and DC.Foxp3-induced Tregs in preventing immune-mediated pathologies.
Main Methods:
- Adenovirus-mediated ectopic expression of Foxp3 in human DCs.
- In vitro stimulation of naive and memory T cells with DC.Foxp3 versus control DCs.
- Assessment of T-cell proliferation, cytokine production (IFN-gamma), and Treg induction.
- Pharmacological modulation using 1-methyl-tryptophan and anti-TGF-beta1 antibodies.
Main Results:
- DC.Foxp3 significantly limited T-cell proliferation and type-1 immune responses in naive T cells.
- DC.Foxp3 enhanced type-2 and Treg responses compared to control DCs.
- Induced CD4(+)CD25(+) Treg cells potently suppressed CD4(+) and CD8(+) T-cell responses.
- Immunosuppressive effects of DC.Foxp3 were reversed by inhibiting TGF-beta1 signaling.
Conclusions:
- Ectopic Foxp3 expression in DCs generates regulatory APCs with potent immunosuppressive capabilities.
- DC.Foxp3 and DC.Foxp3-induced Tregs show promise as therapeutic agents for transplantation and autoimmunity.
- TGF-beta1 signaling is critical for the immunosuppressive function of DC.Foxp3.
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