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© Research
Publication : Blood

Combined deficiency in IkappaBalpha and IkappaBepsilon reveals a critical window of NF-kappaB activity in natural killer cell differentiation

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Blood - 05 Feb 2004

Samson SI, Mémet S, Vosshenrich CA, Colucci F, Richard O, Ndiaye D, Israël A, Di Santo JP

Link to Pubmed [PMID] – 14764534

Blood 2004 Jun;103(12):4573-80

Nuclear factor kappaB (NF-kappaB) transcription factors are key regulators of immune, inflammatory, and acute-phase responses and are also implicated in the control of cell proliferation and apoptosis. While perturbations in NF-kappaB activity impact strongly on B- and T-cell development, little is known about the role for NF-kappaB in natural killer (NK) cell differentiation. Inhibitors of NF-kappaB (IkappaBs) act to restrain NF-kappaB activation. We analyzed the cell-intrinsic effects of deficiencies in 2 IkappaB members (IkappaBalpha and IkappaBepsilon) on NK cell differentiation. Neither IkappaBalpha nor IkappaBepsilon deficiency had major effects on NK cell generation, while their combined absence led to NF-kappaB hyperactivation, resulting in reduced NK cell numbers, incomplete NK cell maturation, and defective interferon gamma (IFN-gamma) production. Complementary analysis of transgenic mice expressing an NF-kappaB-responsive reporter gene showed increased NF-kappaB activity at the stage of NK cell development corresponding to the partial block observed in IkappaBalpha x IkappaBepsilon-deficient mice. These results define a critical window in NK cell development in which NF-kappaB levels may be tightly controlled.

http://www.ncbi.nlm.nih.gov/pubmed/14764534