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NFATc1 induction in peripheral T and B lymphocytes
Matthias Hock1, Martin Vaeth, Ronald Rudolf
1Department of Molecular Pathology, Institute of Pathology, University of Würzburg, D-97080 Würzburg, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|February 1, 2013
Summary
The NFATc1/αA transcription factor, crucial for lymphocyte function, is regulated post-transcriptionally. Its expression impacts T and B cell proliferation and survival, with varying induction levels across immune cell types.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Nuclear Factor of Activated T-cells (NFAT) transcription factors regulate lymphocyte proliferation and survival.
- The NFATc1/αA isoform, induced by immune receptor stimulation, promotes T and B cell proliferation and inhibits activation-induced cell death.
- Understanding NFATc1 regulation is key to controlling adaptive immune responses.
Purpose of the Study:
- To investigate the expression pattern of the Nfatc1 gene locus using novel bacterial artificial chromosome transgenic mice.
- To determine the role of NFATc1/αA in lymphocyte proliferation, survival, and activation-induced cell death.
- To elucidate the regulatory mechanisms of Nfatc1 gene induction.
Main Methods:
- Generation and analysis of Nfatc1/Egfp bacterial artificial chromosome transgenic mice.
- Flow cytometry to assess EGFP expression in various immune cell populations.
- In vitro stimulation assays using anti-CD3/CD28 for T cells and anti-IgM, anti-CD40, LPS, CpG for B cells.
- Quantitative analysis of NFATc1/αA RNA and protein levels.
Main Results:
- Nfatc1/Egfp expression is detected early in thymocytes and nonstimulated peripheral T and B cells.
- Immune receptor stimulation elevates Nfatc1/Egfp in B, Th1, and Th2 cells, but weakly in T regulatory, Th9, and Th17 cells.
- NFATc1/αA protein levels increase significantly more than RNA levels upon stimulation, suggesting post-transcriptional regulation.
- Anti-IgM stimulation induces NFATc1/αA and proliferation in B cells, but also activation-induced cell death, which is suppressed by co-stimulatory signals.
- Co-stimulatory signals (anti-CD40, LPS, CpG) enhance NFATc1/αA generation alongside NF-κB factors.
Conclusions:
- The Nfatc1 gene acts as a primary response gene, with its induction primarily regulated at the post-transcriptional level.
- NFATc1/αA plays a differential role in T and B cell responses, influencing proliferation, survival, and cell death.
- Understanding NFATc1 regulation provides insights into controlling adaptive immunity and preventing autoimmune diseases.
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