title: TSC-22 Promotes Interleukin-2-Deprivation Induced Apoptosis in T-Lymphocytes.
abstract: Originally described as a TGF-β-inducible gene, tsc-22 (Transforming growth factor-beta Stimulated Clone 22) encodes a transcriptional regulator affecting biological processes such as cell growth, differentiation, or apoptosis. Along with GILZ (Glucocorticoid-Induced Leucine Zipper), TSC-22 belongs to the evolutionary conserved TSC-22 Domain family. We previously showed that, in T-lymphocytes, GILZ expression was induced upon IL-2 withdrawal, delaying apoptosis through down-regulation of the pro-apoptotic protein BIM expression. The aim of this work was then to elucidate the respective roles of GILZ and TSC-22 upon IL-2 deprivation-induced apoptosis. We report here that these two highly homologous genes are concomitantly expressed in most human tissues and in primary T-lymphocytes and that expression of TSC-22 promotes T-lymphocytes apoptosis by inhibiting GILZ functions. Indeed, we demonstrated that TSC-22 expression in the murine lymphoid CTLL-2 cell line promoted IL-2 deprivation-induced apoptosis. BIM expression and caspases-9 and -3 activities were markedly increased in TSC-22 expressing clones compared to control clones. Analysis of GILZ expression revealed that TSC-22 prevented the induction of the GILZ protein upon IL-2 deprivation, by inhibiting gilz mRNA transcription. These results suggested that TSC-22 could counteract the protective effect of GILZ on IL-2-deprivation-induced apoptosis. Moreover, TSC-22-induced inhibition of GILZ expression was also found in CTLL-2 cells treated with glucocorticoids or TGF-β. In the human NKL cell line deprived of IL-2, TSC-22 showed the same effect and thus may represent a potent repressor of GILZ expression in IL-2-dependent cells, independently of the cell type, or the stimulus, leading to an increase of IL-2-deprived T-cells apoptosis. J. Cell. Biochem. 117: 1855-1868, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: UMR 996-Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, 92296, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Pépin
authors.affiliation: UMR 996-Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, 92296, France.
authors.forename: Marie-Alix
authors.initials: MA
authors.lastname: Espinasse
authors.affiliation: UMR 996-Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, 92296, France.
authors.forename: Perle
authors.initials: P
authors.lastname: Latré de Laté
authors.affiliation: UMR 996-Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, 92296, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Szely
authors.affiliation: UMR 996-Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, 92296, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: UMR 996-Inflammation, Chemokines and Immunopathology, Inserm, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, 92296, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Biola-Vidamment
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D051379:Mice; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: C498608:Dsip1 protein, mouse; D007376:Interleukin-2; D012097:Repressor Proteins; C490983:Tgfb1i4 protein, mouse; D014157:Transcription Factors
keywords: APOPTOSIS; BIM; GILZ; IL-2 DEPRIVATION; T-LYMPHOCYTES; TSC-22