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Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
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Rbpj expression in regulatory T cells is critical for restraining TH2 responses
Michael Delacher1,2,3, Christian Schmidl2, Yonatan Herzig4
1Chair for Immunology, University Regensburg and University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Nature Communications
|April 10, 2019
Summary
Regulatory T cells (Treg) require Rbpj to control T helper 2 (TH2) responses. Deleting Rbpj in Treg cells impairs TH2 control, leading to immune disorders and TH2-like differentiation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The transcriptional regulator Rbpj plays a role in T-helper (TH) subset polarization.
- Its specific function within regulatory T (Treg) cells is not well understood.
Purpose of the Study:
- To investigate the function of Rbpj in Treg cells.
- To elucidate the role of Rbpj in Treg-mediated immune regulation.
Main Methods:
- Treg-specific Rbpj deletion in mice.
- Analysis of immune cell populations, including Treg cells, T-helper subsets, and B cells.
- Assessment of germinal center formation and immunoglobulin class switching.
- Chromatin landscape and gene expression profiling.
- Induction of phenotype by parasitic nematode infection.
Main Results:
- Treg-specific Rbpj deletion caused splenomegaly and lymphadenopathy.
- Rbpj-deficient Treg cells showed impaired control of TH2 polarization and B cell responses.
- Spontaneous germinal center formation and TH2-associated immunoglobulin class switching were observed.
- The phenotype was environment-dependent and exacerbated by parasitic nematode infection.
- Rbpj-deficient Treg cells exhibited open chromatin and gene expression profiles similar to tissue-derived TH2-polarized Treg cells, with a Gata-3 signature.
Conclusions:
- Treg cells require Rbpj to effectively restrain TH2 responses.
- Rbpj is crucial for preventing excessive TH2-like differentiation within Treg cells.
- Dysregulation of Rbpj in Treg cells can lead to autoimmune or inflammatory conditions.
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