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Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development

Guo, Fukun, Cancelas, Jose A., Hildeman, David, Williams, David A., Zheng, Yi·2008·Blood
DOI 10.1182/blood-2008-01-132068
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Abstract

Rac GTPases have been implicated in the regulation of diverse functions in various blood cell lineages, but their role in T-cell development is not well understood. We have carried out conditional gene targeting to achieve hematopoietic stem cell (HSC)– or T-cell lineage–specific deletion of Rac1 or Rac1/Rac2 by crossbreeding the Mx-Cre or Lck-Cre transgenic mice with Rac1loxp/loxp or Rac1loxp/loxp;Rac2−/− mice. We found that (1) HSC deletion of both Rac1 and Rac2 inhibited production of common lymphoid progenitors (CLPs) in bone marrow and suppressed T-cell development in thymus and peripheral organs, whereas deletion of Rac1 moderately affected CLP production and T-cell development. (2) T cell–specific deletion of Rac1 did not affect T-cell development, whereas deletion of both Rac1 and Rac2 reduced immature CD4+CD8+ and mature CD4+ populations in thymus as well as CD4+ and CD8+ populations in spleen. (3) The developmental defects of Rac1/Rac2 knockout T cells were associated with proliferation, survival, adhesion, and migration defects. (4) Rac1/Rac2 deletion suppressed T-cell receptor–mediated proliferation, IL-2 production, and Akt activation in thymocytes. Thus, Rac1 and Rac2 have unique roles in CLP production and share a redundant but essential role in later stages of T-cell development by regulating survival and proliferation signals.

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Cited by

Metadata

Authors
Guo, F., Cancelas, J. A., Hildeman, D., Williams, D. A., & Zheng, Y.
Affiliations
Divisions of Experimental Hematology and Cancer Biology, and Immunobiology, Children's Hospital Medical Center, and
Venue
Blood
Publisher
American Society of Hematology
Published
2008-09-01
Volume
112
Issue
5
Pages
1767-1775
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2008-01-132068
Cited by
100
References
1
Language
en

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