Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice
Abstract
APCs are essential for innate and adaptive immunity as well as self-immune tolerance. Here, we show that the Cap'n'collar member Bach1 regulates the generation of APCs, specifically macrophages and dendritic cells, in mice. The impaired APC development in Bach1^(-/-) mice was accompanied by defects in downstream T-cell responses and partial protection from experimental autoimmune encephalomyelitis. Genomewide analyses identified a panel of Bach1 target genes and ablation of the direct Bach1 target gene HO-1 exacerbated the impaired APC development observed in Bach1^(-/-) mice. This was attributed to the impaired ability of HO-1^(-/-)Bach1^(-/-) double mutants to produce upstreamAPC progenitor cells, including common myeloid progenitor (CMP)–Flk2^+. By contrast, we observed an increase in hematopoietic stem-progenitor cells (HSPCs) in these mice, suggesting a developmental block in the progression of HSPCs to CMP-Flk2^+ and subsequently APCs.
Additional Information
© 2012 by The American Society of Hematology. Submitted April 25, 2012; accepted July 7, 2012. Prepublished online as Blood First Edition paper, July 12, 2012. The authors thank Dr Kazuhiko Igarashi for sharing the Bach1^(-/-) mice and are grateful to Alex Balazs and Michael Bethune for helpful critiques of the manuscript. This work was supported by the National Institutes of Health (grants 5P01CA132681-02 and 5R01AI093531-02 to D.B. and grant F32 CA139883 to A.Y.-L.S.). Authorship: Contribution: A.Y.-L.S., Y.G.-F., A. Minisandram, A. Martin, and K.T. performed the experiments; A.Y.-L.S., M.B., and D.B. conceived the study; A.Y.-L.S., Y.G.-F., A. Mehta, A.Y.-L.S., K.T., M.B., and D.B. provided crucial reagents; A.Y.-L.S. and D.B. wrote the manuscript; and all authors provided input on the manuscript. Conflict-of-interest disclosure: The authors declare no competing financial interests. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734.Attached Files
Published - Blood-2012-So-2428-37.pdf
Supplemental Material - blood-2012-04-426247-1.pdf
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Additional details
- PMCID
- PMC3448256
- Eprint ID
- 35345
- Resolver ID
- CaltechAUTHORS:20121107-154121628
- NIH
- 5P01CA132681-02
- NIH
- 5R01AI093531-02
- NIH Postdoctoral Fellowship
- F32 CA139883
- Created
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2012-11-08Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field