Helios deficiency has minimal impact on T cell development and function.
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.
Cai
Qi
Q
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.
Dierich
Andrée
A
Oulad-Abdelghani
Mustapha
M
Chan
Susan
S
Kastner
Philippe
P
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
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