| First Author | Mankan AK | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 16 | Pages | 6567-72 |
| PubMed ID | 21464320 | Mgi Jnum | J:171365 |
| Mgi Id | MGI:4949794 | Doi | 10.1073/pnas.1018331108 |
| Citation | Mankan AK, et al. (2011) TNF-{alpha}-dependent loss of IKK{beta}-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis. Proc Natl Acad Sci U S A 108(16):6567-72 |
| abstractText | Loss of IkappaB kinase (IKK) beta-dependent NF-kappaB signaling in hematopoietic cells is associated with increased granulopoiesis. Here we identify a regulatory cytokine loop that causes neutrophilia in Ikkbeta-deficient mice. TNF-alpha-dependent apoptosis of myeloid progenitor cells leads to the release of IL-1beta, 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 Ikkbeta-deficient animals more susceptible to the development of experimental autoimmune encephalitis. These results unravel so far unanticipated direct and indirect functions for IKKbeta in myeloid progenitor survival and maintenance of innate and Th17 immunity and raise concerns about long-term IKKbeta inhibition in IL-17-mediated diseases. |
