Related Experiment Video
Updated: Jun 17, 2026
10:27
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
c-Rel but not NF-kappaB1 is important for T regulatory cell development
Elissa K Deenick1, Alisha R Elford, Marc Pellegrini
1Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ont., Canada.
European Journal of Immunology
|January 19, 2010
Summary
Regulatory T (Treg) cell development is crucial for immune tolerance. This study reveals that c-Rel, a member of the NF-kappaB family, is essential for Treg cell homeostasis, while NF-kappaB1 is not.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- Regulatory T (Treg) cells are vital for maintaining peripheral tolerance and controlling immune responses.
- Treg cell generation in the thymus depends on T-cell receptor (TCR) triggering and CD28 costimulation, activating signaling pathways like NF-kappaB.
- Previous research highlighted the importance of PKCtheta, Bcl-10, and CARMA1 in Treg development.
Purpose of the Study:
- To investigate the specific roles of different NF-kappaB family members in Treg cell development and homeostasis.
- To elucidate the T-cell intrinsic requirements for key signaling molecules in Treg cell generation.
Main Methods:
- Utilized knockout (KO) animal models lacking specific NF-kappaB family members.
- Employed mixed bone marrow chimeras to assess T-cell intrinsic requirements.
- Analyzed Treg cell numbers and function in WT and KO chimeric settings.
Main Results:
- Treg cell numbers were significantly reduced in mice lacking c-Rel, but not NF-kappaB1 (p50).
- Bone marrow chimera experiments demonstrated that the requirement for PKCtheta, Bcl-10, and c-Rel is intrinsic to T cells.
- The presence of wild-type (WT) cells could not rescue the Treg cell deficiency in KO chimeras.
Conclusions:
- c-Rel plays a critical role in Treg cell development and homeostasis.
- NF-kappaB1 (p50) does not appear to have a significant role in Treg cell development.
- These findings highlight the differential contributions of NF-kappaB family members to Treg cell biology.
Related Concept Videos
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...