Kreisel, D., Sugimoto, S., Tietjens, J., Zhu, J., Yamamoto, S., Krupnick, A.S., Carmody, R.J. and Gelman, A.E. (2011) Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. Journal of Clinical Investigation, 121(1), pp. 265-276. (doi: 10.1172/JCI42596)
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Abstract
Granulocytes are pivotal regulators of tissue injury. However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood. Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency (i.e., inflammatory) conditions, but not homeostatic conditions. Treatment of mouse myeloid progenitors with G-CSF — serum concentrations of which rise under inflammatory conditions — rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner. Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-κB p50–dependent manner. In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage. These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Carmody, Dr Ruaidhri |
Authors: | Kreisel, D., Sugimoto, S., Tietjens, J., Zhu, J., Yamamoto, S., Krupnick, A.S., Carmody, R.J., and Gelman, A.E. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Clinical Investigation |
Journal Abbr.: | JCI |
ISSN: | 0021-9738 |
ISSN (Online): | 1558-8238 |
Published Online: | 13 December 2010 |
Copyright Holders: | Copyright © 2011 Americal Society for Clinical Investigation |
First Published: | First published in Journal of Clinical Investigation 121(1):265-276 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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