TNF-alpha-dependent loss of IKKbeta-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis.

Détails

ID Serval
serval:BIB_40B6E0D2BD63
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TNF-alpha-dependent loss of IKKbeta-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Mankan A.K., Canli O., Schwitalla S., Ziegler P., Tschopp J., Korn T., Greten F.R.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2011
Volume
108
Numéro
16
Pages
6567-6572
Langue
anglais
Résumé
Loss of IκB kinase (IKK) β-dependent NF-κB signaling in hematopoietic cells is associated with increased granulopoiesis. Here we identify a regulatory cytokine loop that causes neutrophilia in Ikkβ-deficient mice. TNF-α-dependent apoptosis of myeloid progenitor cells leads to the release of IL-1β, which promotes Th17 polarization of peripheral CD4(+) T cells. Although the elevation of IL-17 and the consecutive induction of granulocyte colony-stimulating factor compensate for the loss of myeloid progenitor cells, the facilitated induction of Th17 cells renders Ikkβ-deficient animals more susceptible to the development of experimental autoimmune encephalitis. These results unravel so far unanticipated direct and indirect functions for IKKβ in myeloid progenitor survival and maintenance of innate and Th17 immunity and raise concerns about long-term IKKβ inhibition in IL-17-mediated diseases.
Mots-clé
Animals, Apoptosis/genetics, Apoptosis/immunology, Autoimmune Diseases of the Nervous System/genetics, Autoimmune Diseases of the Nervous System/immunology, Encephalitis/genetics, Encephalitis/immunology, I-kappa B Kinase/genetics, I-kappa B Kinase/immunology, Immunity, Innate/genetics, Immunity, Innate/immunology, Interleukin-17/biosynthesis, Interleukin-17/genetics, Interleukin-1beta/biosynthesis, Interleukin-1beta/genetics, Mice, Mice, Knockout, Myeloid Progenitor Cells/immunology, Myeloid Progenitor Cells/metabolism, Myelopoiesis/genetics, Myelopoiesis/immunology, NF-kappa B/genetics, NF-kappa B/immunology, Signal Transduction/genetics, Signal Transduction/immunology, Th17 Cells/immunology, Th17 Cells/metabolism, Tumor Necrosis Factor-alpha/biosynthesis, Tumor Necrosis Factor-alpha/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/09/2011 9:59
Dernière modification de la notice
08/05/2019 17:38
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