title: TCR and IL-7 Signaling Are Altered in the Absence of Functional GTPase of the Immune Associated Nucleotide Binding Protein 5 (GIMAP5).
abstract: GTPase of the immune associated nucleotide binding protein (GIMAP) family of proteins are expressed essentially in cells of the hematopoietic system. Mutation in the founding member of this gene family, Gimap5, results in the lymphopenic phenotype in Bio-Breeding diabetes prone rats. In mice, deletion of functional Gimap5 gene affects the survival and renewal of hematopoietic stem cells in addition to the defects observed in T cells. Here we show that T cells from OTII TCR-transgenic Gimap5sph/sph mice do not proliferate in response to its cognate antigen. Furthermore, T cells from Gimap5 mutant rats and mice show decreased phosphorylation of STAT5 following stimulation with IL-7. Our results suggest that functional Gimap5 is required for optimal signaling through TCR and IL-7R in T cells.
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Ghobadi
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Marian
authors.initials: M
authors.lastname: Mayhue
authors.affiliation: Department of Pediatrics, Division of Cellular and Molecular Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, United States of America.
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.|Centre de recherche clinique, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.|Centre de recherche clinique, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D015851:Interleukin-7 / Q000378:metabolism*; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017252:CD3 Complex; C534135:Gimap5 protein, mouse; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D050799:STAT5 Transcription Factor; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C494977:Gimap5 protein, rat