Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis

Daniel Kreisel, Seiichiro Sugimoto, Jeremy Tietjens, Jihong Zhu, Sumiharu Yamamoto, Alexander S. Krupnick, Ruaidhri J. Carmody, Andrew E. Gelman

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)265-276
Number of pages12
JournalJournal of Clinical Investigation
Volume121
Issue number1
DOIs
Publication statusPublished - Jan 4 2011
Externally publishedYes

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B-Cell Leukemia
Acute Lung Injury
B-Cell Lymphoma
Emergencies
Granulocyte Colony-Stimulating Factor
Granulocytes
Transplants
Lung Injury
Reperfusion Injury
Lung
Wounds and Injuries
Serum

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kreisel, D., Sugimoto, S., Tietjens, J., Zhu, J., Yamamoto, S., Krupnick, A. S., ... Gelman, A. E. (2011). Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. Journal of Clinical Investigation, 121(1), 265-276. https://doi.org/10.1172/JCI42596

Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. / Kreisel, Daniel; Sugimoto, Seiichiro; Tietjens, Jeremy; Zhu, Jihong; Yamamoto, Sumiharu; Krupnick, Alexander S.; Carmody, Ruaidhri J.; Gelman, Andrew E.

In: Journal of Clinical Investigation, Vol. 121, No. 1, 04.01.2011, p. 265-276.

Research output: Contribution to journalArticle

Kreisel, D, Sugimoto, S, Tietjens, J, Zhu, J, Yamamoto, S, Krupnick, AS, Carmody, RJ & Gelman, AE 2011, 'Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis', Journal of Clinical Investigation, vol. 121, no. 1, pp. 265-276. https://doi.org/10.1172/JCI42596
Kreisel, Daniel ; Sugimoto, Seiichiro ; Tietjens, Jeremy ; Zhu, Jihong ; Yamamoto, Sumiharu ; Krupnick, Alexander S. ; Carmody, Ruaidhri J. ; Gelman, Andrew E. / Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 1. pp. 265-276.
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