TNF-α–dependent loss of IKKβ-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis
| العنوان: | TNF-α–dependent loss of IKKβ-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis |
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| المؤلفون: | Jürg Tschopp, Arun K. Mankan, Florian R. Greten, Thomas Korn, Sarah Schwitalla, Paul Ziegler, Özge Canli |
| المصدر: | Proceedings of the National Academy of Sciences. 108:6567-6572 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Myeloid, medicine.medical_treatment, Interleukin-1beta, Apoptosis, IκB kinase, Biology, Mice, Autoimmune Diseases of the Nervous System, medicine, Animals, Progenitor cell, Myeloid Progenitor Cells, Interleukin 3, Mice, Knockout, Myelopoiesis, Multidisciplinary, Tumor Necrosis Factor-alpha, Interleukin-17, NF-kappa B, Granulocytosis, Biological Sciences, medicine.disease, Immunity, Innate, I-kappa B Kinase, Haematopoiesis, medicine.anatomical_structure, Cytokine, Immunology, Cancer research, Encephalitis, Th17 Cells, Signal Transduction |
| الوصف: | 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. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b5794630bf83065a8f06b746c421fc3 https://doi.org/10.1073/pnas.1018331108 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2b5794630bf83065a8f06b746c421fc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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