Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program.
Yohei Sato1, Erika Osada1, Yoshinobu Manome1
1Core Research Facilities, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
Heliyon
|December 21, 2023
Summary
Non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) signaling, specifically NFKB2, is crucial for maintaining the function and phenotype of human regulatory T cells (Tregs) via FOXP3.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Regulatory T cells (Tregs) are essential for immune system balance.
- The role of non-canonical nuclear factor 'κ-light-chain-enhancer' of activated B cells (NFKB) signaling in human Tregs remains unclear.
Purpose of the Study:
- To investigate the function of NFKB signaling pathways in human Tregs.
- To elucidate the role of NFKB2 in maintaining Treg phenotype and function.
Main Methods:
- Genetic modification of a Treg-like cell line (MT-2) and primary human Tregs using CRISPR/Cas9.
- Analysis of FOXP3 expression and FOXP3-dependent molecules.
- Assessment of Treg suppressive function.
Main Results:
- NFKB2 knockout in MT-2 cells and human Tregs led to FOXP3 downregulation.
- NFKB2 knockout reduced expression of FOXP3-dependent molecules.
- NFKB2 knockout human Tregs exhibited diminished suppressive function.
Conclusions:
- Non-canonical NFKB signaling, particularly NFKB2, is vital for maintaining the Treg phenotype and suppressive function.
- This maintenance is achieved through the FOXP3-dependent regulatory T cell program.
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