Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint |
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Authors: | Norimasa Tamehiro Hiroyo Oda Mutsunori Shirai Harumi Suzuki |
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Institution: | 1. Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.; 2. Department of Microbiology, Yamaguchi University School of Medicine, Ube, Japan.; INSERM-Université Paris-Sud, FRANCE, |
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Abstract: | RhoH, an atypical small Rho-family GTPase, critically regulates thymocyte differentiation through the coordinated interaction with Lck and Zap70. Therefore, RhoH deficiency causes defective T cell development, leading to a paucity of mature T cells. Since there has been no gain-of-function study on RhoH before, we decided to take a transgenic approach to assess how the overexpression of RhoH affects the development of T cells. Although RhoH transgenic (RhoHtg) mice expressed three times more RhoH protein than wild-type mice, β-selection, positive, and negative selection in the thymus from RhoHtg mice were unaltered. However, transgenic introduction of RhoH into Rag2 deficient mice resulted in the generation of CD4+CD8+ (DP) thymocytes, indicating that overexpression of RhoH could bypass β-selection without TCRβ gene rearrangement. This was confirmed by the in vitro development of DP cells from Rag2-/-RhoHtg DN3 cells on TSt-4/Dll-1 stroma in an Lck dependent manner. Collectively, our results indicate that an excess amount of RhoH is able to initiate pre-TCR signaling in the absence of pre-TCR complexes. |
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