T lymphocytes play a central role in controlling adaptive immune responses. IL-2 critically regulates both T cell growth and death and is involved in maintaining peripheral tolerance, but the molecules involved in these and other IL-2 actions are only partially known. We now provide a comprehensive compendium of the genes expressed in T cells and of those regulated by IL-2 based on a combination of DNA microarrays and serial analysis of gene expression (SAGE). The newly identified IL-2 target genes include many genes previously linked to apoptosis in other cellular systems that may contribute to IL-2-dependent survival functions. We also studied the mRNA expression of known regulators of signaling pathways for their induction in response to IL-2 in order to identify potential novel positive and/or negative feedback regulators of IL-2 signaling. We show that IL-2 regulates only a limited number of these genes. These include suppressors of cytokine signaling (SOCS) 1, SOCS2, dual-specificity phosphatase (DUSP) 5, DUSP6 and non-receptor type phosphatase-7 (PTPN7). Additionally, we provide evidence that many genes expressed in T cells locate in chromosomal clusters, and that select IL-2-regulated genes are located in at least two clusters, one at 5q31, a known cytokine gene cluster, and the other at 6p21.3, a region that contains genes encoding the tumor necrosis factor (TNF) superfamily members TNF, LT-alpha and LT-beta.

Kovanen, P.e., Young, L., Al-Shami, A., Rovella, V., Pise-Masison, C.a., Radonovich, M.f., et al. (2005). Global analysis of IL-2 target genes: identification of chromosomal clusters of expressed genes. INTERNATIONAL IMMUNOLOGY, 17(8), 1009-1021 [10.1093/intimm/dxh283].

Global analysis of IL-2 target genes: identification of chromosomal clusters of expressed genes

Rovella, Valentina;
2005

Abstract

T lymphocytes play a central role in controlling adaptive immune responses. IL-2 critically regulates both T cell growth and death and is involved in maintaining peripheral tolerance, but the molecules involved in these and other IL-2 actions are only partially known. We now provide a comprehensive compendium of the genes expressed in T cells and of those regulated by IL-2 based on a combination of DNA microarrays and serial analysis of gene expression (SAGE). The newly identified IL-2 target genes include many genes previously linked to apoptosis in other cellular systems that may contribute to IL-2-dependent survival functions. We also studied the mRNA expression of known regulators of signaling pathways for their induction in response to IL-2 in order to identify potential novel positive and/or negative feedback regulators of IL-2 signaling. We show that IL-2 regulates only a limited number of these genes. These include suppressors of cytokine signaling (SOCS) 1, SOCS2, dual-specificity phosphatase (DUSP) 5, DUSP6 and non-receptor type phosphatase-7 (PTPN7). Additionally, we provide evidence that many genes expressed in T cells locate in chromosomal clusters, and that select IL-2-regulated genes are located in at least two clusters, one at 5q31, a known cytokine gene cluster, and the other at 6p21.3, a region that contains genes encoding the tumor necrosis factor (TNF) superfamily members TNF, LT-alpha and LT-beta.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/09
Settore MED/03
English
genomics
microarray
target gene
SAGE
interleukin-2
Animals
Cells, Cultured
Chromosomes, Human
DNA-Binding Proteins
Feedback
Gene Expression Profiling
Gene Expression Regulation
Humans
Interleukin-2
Mice
Mice, Knockout
Milk Proteins
Oligonucleotide Array Sequence Analysis
STAT5 Transcription Factor
Signal Transduction
T-Lymphocytes
Trans-Activators
Multigene Family
Kovanen, P.e., Young, L., Al-Shami, A., Rovella, V., Pise-Masison, C.a., Radonovich, M.f., et al. (2005). Global analysis of IL-2 target genes: identification of chromosomal clusters of expressed genes. INTERNATIONAL IMMUNOLOGY, 17(8), 1009-1021 [10.1093/intimm/dxh283].
Kovanen, Pe; Young, L; Al-Shami, A; Rovella, V; Pise-Masison, Ca; Radonovich, Mf; Powell, J; Fu, J; Brady, Jn; Munson, Pj; Leonard, Wj
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/308719
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