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

Details

Serval ID
serval:BIB_40B6E0D2BD63
Type
Article: article from journal or magazin.
Collection
Publications
Title
TNF-alpha-dependent loss of IKKbeta-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(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
Publication state
Published
Issued date
2011
Volume
108
Number
16
Pages
6567-6572
Language
english
Abstract
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.
Keywords
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
Yes
Create date
02/09/2011 9:59
Last modification date
20/08/2019 14:39
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