title: Helios deficiency has minimal impact on T cell development and function.
abstract: Helios is a member of the Ikaros family of zinc finger transcription factors. It is expressed mainly in T cells, where it associates with Ikaros-containing complexes and has been proposed to act as a rate-limiting factor for Ikaros function. Overexpression of wild-type or dominant-negative Helios isoforms profoundly alters alphabeta T cell differentiation and activation, and endogenous Helios is expressed at strikingly high levels in regulatory T cells. Helios has also been implicated as a tumor suppressor in human T cell acute lymphoblastic leukemias. These studies suggest a central role for Helios in T cell development and homeostasis, but whether this protein is physiologically required in T cells is unclear. We report herein that inactivation of the Helios gene by homologous recombination does not impair the differentiation and effector cell function of alphabeta and gammadelta T cells, NKT cells, and regulatory T cells. These results suggest that Helios is not essential for T cells, and that its function can be compensated for by other members of the Ikaros family.
authors.affiliation: Department of Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM Unité 964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Illkirch, France.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cai
authors.forename: Andrée
authors.initials: A
authors.lastname: Dierich
authors.forename: Mustapha
authors.initials: M
authors.lastname: Oulad-Abdelghani
authors.forename: Susan
authors.initials: S
authors.lastname: Chan
authors.forename: Philippe
authors.initials: P
authors.lastname: Kastner
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D020868:Gene Silencing / Q000276:immunology; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D005810:Multigene Family / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; C491746:Zfpn1a2 protein, mouse; D051740:Ikaros Transcription Factor