title: Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint.
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.
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Tamehiro
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Oda
authors.affiliation: Department of Microbiology, Yamaguchi University School of Medicine, Ube, Japan.
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Shirai
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019672:Genes, T-Cell Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; C496930:RhoH protein, mouse; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins