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Combined deficiency in IκBα and IκBϵ reveals a critical window of NF-κB activity in natural killer cell differentiation

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03109750
Contributor : Christian Vosshenrich <>
Submitted on : Wednesday, January 13, 2021 - 11:06:48 PM
Last modification on : Wednesday, February 17, 2021 - 10:11:08 AM

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Sandrine Samson, Sylvie Mémet, Christian A. J. Vosshenrich, Francesco Colucci, Odile Richard, et al.. Combined deficiency in IκBα and IκBϵ reveals a critical window of NF-κB activity in natural killer cell differentiation. Blood, American Society of Hematology, 2004, 103 (12), pp.4573-4580. ⟨10.1182/blood-2003-08-2975⟩. ⟨pasteur-03109750⟩

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