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10:31
Real-time Live Imaging of T-cell Signaling Complex Formation
Published on: June 23, 2013
Mature T cells depend on signaling through the IKK complex
Marc Schmidt-Supprian1, Gilles Courtois, Jane Tian
1Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Immunity
|September 23, 2003
Summary
The IkappaB kinase (IKK) complex is vital for T cell survival and function. Specifically, IKK2 is crucial for developing regulatory and memory T cells, while NEMO or kinase-dead IKK2 prevents peripheral T cell development.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The transcription factor NF-kappaB plays a key role in T cell development and function.
- The IkappaB kinase (IKK) complex, comprising IKK1/alpha, IKK2/beta, and NEMO/IKKgamma, activates NF-kappaB.
- Previous studies suggested IKK1 and IKK2 are dispensable for T cell development.
Purpose of the Study:
- To investigate the specific roles of IKK2 and NEMO in T cell development and function.
- To determine the necessity of IKK-induced NF-kappaB activation for mature T cell generation and survival.
Main Methods:
- T lineage-specific deletion of IKK2.
- T cell-specific ablation of NEMO.
- Replacement of IKK2 with a kinase-dead mutant.
- Adoptive transfer experiments.
Main Results:
- T lineage-specific deletion of IKK2 permitted naive T cell survival but impaired regulatory and memory T cell generation.
- T cell-specific ablation of NEMO or use of kinase-dead IKK2 prevented peripheral T cell development.
- IKK-induced NF-kappaB activation is essential for mature T cell generation and survival.
Conclusions:
- IKK-induced NF-kappaB activation, via IKK1 or IKK2, is essential for mature T cell generation and survival.
- IKK2 plays an additional, critical role in the development of regulatory and memory T cells.
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