Regulation of the IL-21 Gene by the NF-kappa B Transcription Factor c-Rel

Guobing Chen, Kristine Hardy, Karen Bunting, Stephen Stephen, Lina Ma, Frances Shannon

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

IL-21 is a member of the common γ-chain–dependent cytokine family and is a key modulator of lymphocyte development, proliferation, and differentiation. IL-21 is highly expressed in activated CD4+ T cells and plays a critical role in the expansion and differentiation of the Th cell subsets, Th17 and follicular helper T (TFH) cells. Because of its potent activity in both myeloid and lymphoid cell immune responses, it has been implicated in a number of autoimmune diseases and has also been used as a therapeutic agent in the treatment of some cancers. In this study, we demonstrate that c-Rel, a member of the NF-κB family of transcription factors, is required for IL-21 gene expression in T lymphocytes. IL-21 mRNA and protein levels are reduced in the CD4+ cells of rel−/− mice when compared with rel+/+ mice in both in vitro and in vivo models. A c-Rel binding site identified in the proximal promoter of il21 is confirmed to bind c-Rel in vitro and in vivo and to regulate expression from the il21 promoter in T cells. Downstream of IL-21 expression, Th17, TFH, and germinal center B cell development are also impaired in rel−/− mice. The administration of IL-21 protein rescued the development of TFH cells but not germinal center B cells. Taken together, c-Rel plays an important role in the expression of IL-21 in T cells and subsequently in IL-21-dependent TFH cell development
Original languageEnglish
Pages (from-to)2350-2359
Number of pages10
JournalJournal of Immunology
Volume185
Issue number4
DOIs
Publication statusPublished - 2010
Externally publishedYes

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NF-kappa B
Transcription Factors
Genes
Helper-Inducer T-Lymphocytes
T-Lymphocytes
Germinal Center
B-Lymphocytes
interleukin-21
3'-(1-butylphosphoryl)adenosine
Lymphocytes
Th17 Cells
Myeloid Cells
Autoimmune Diseases
Cell Differentiation
Proteins
Binding Sites
Cytokines
Gene Expression
Messenger RNA

Cite this

Chen, G., Hardy, K., Bunting, K., Stephen, S., Ma, L., & Shannon, F. (2010). Regulation of the IL-21 Gene by the NF-kappa B Transcription Factor c-Rel. Journal of Immunology, 185(4), 2350-2359. https://doi.org/10.4049/jimmunol.1000317
Chen, Guobing ; Hardy, Kristine ; Bunting, Karen ; Stephen, Stephen ; Ma, Lina ; Shannon, Frances. / Regulation of the IL-21 Gene by the NF-kappa B Transcription Factor c-Rel. In: Journal of Immunology. 2010 ; Vol. 185, No. 4. pp. 2350-2359.
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abstract = "IL-21 is a member of the common γ-chain–dependent cytokine family and is a key modulator of lymphocyte development, proliferation, and differentiation. IL-21 is highly expressed in activated CD4+ T cells and plays a critical role in the expansion and differentiation of the Th cell subsets, Th17 and follicular helper T (TFH) cells. Because of its potent activity in both myeloid and lymphoid cell immune responses, it has been implicated in a number of autoimmune diseases and has also been used as a therapeutic agent in the treatment of some cancers. In this study, we demonstrate that c-Rel, a member of the NF-κB family of transcription factors, is required for IL-21 gene expression in T lymphocytes. IL-21 mRNA and protein levels are reduced in the CD4+ cells of rel−/− mice when compared with rel+/+ mice in both in vitro and in vivo models. A c-Rel binding site identified in the proximal promoter of il21 is confirmed to bind c-Rel in vitro and in vivo and to regulate expression from the il21 promoter in T cells. Downstream of IL-21 expression, Th17, TFH, and germinal center B cell development are also impaired in rel−/− mice. The administration of IL-21 protein rescued the development of TFH cells but not germinal center B cells. Taken together, c-Rel plays an important role in the expression of IL-21 in T cells and subsequently in IL-21-dependent TFH cell development",
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Chen, G, Hardy, K, Bunting, K, Stephen, S, Ma, L & Shannon, F 2010, 'Regulation of the IL-21 Gene by the NF-kappa B Transcription Factor c-Rel', Journal of Immunology, vol. 185, no. 4, pp. 2350-2359. https://doi.org/10.4049/jimmunol.1000317

Regulation of the IL-21 Gene by the NF-kappa B Transcription Factor c-Rel. / Chen, Guobing; Hardy, Kristine; Bunting, Karen; Stephen, Stephen; Ma, Lina; Shannon, Frances.

In: Journal of Immunology, Vol. 185, No. 4, 2010, p. 2350-2359.

Research output: Contribution to journalArticle

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T1 - Regulation of the IL-21 Gene by the NF-kappa B Transcription Factor c-Rel

AU - Chen, Guobing

AU - Hardy, Kristine

AU - Bunting, Karen

AU - Stephen, Stephen

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AU - Shannon, Frances

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N2 - IL-21 is a member of the common γ-chain–dependent cytokine family and is a key modulator of lymphocyte development, proliferation, and differentiation. IL-21 is highly expressed in activated CD4+ T cells and plays a critical role in the expansion and differentiation of the Th cell subsets, Th17 and follicular helper T (TFH) cells. Because of its potent activity in both myeloid and lymphoid cell immune responses, it has been implicated in a number of autoimmune diseases and has also been used as a therapeutic agent in the treatment of some cancers. In this study, we demonstrate that c-Rel, a member of the NF-κB family of transcription factors, is required for IL-21 gene expression in T lymphocytes. IL-21 mRNA and protein levels are reduced in the CD4+ cells of rel−/− mice when compared with rel+/+ mice in both in vitro and in vivo models. A c-Rel binding site identified in the proximal promoter of il21 is confirmed to bind c-Rel in vitro and in vivo and to regulate expression from the il21 promoter in T cells. Downstream of IL-21 expression, Th17, TFH, and germinal center B cell development are also impaired in rel−/− mice. The administration of IL-21 protein rescued the development of TFH cells but not germinal center B cells. Taken together, c-Rel plays an important role in the expression of IL-21 in T cells and subsequently in IL-21-dependent TFH cell development

AB - IL-21 is a member of the common γ-chain–dependent cytokine family and is a key modulator of lymphocyte development, proliferation, and differentiation. IL-21 is highly expressed in activated CD4+ T cells and plays a critical role in the expansion and differentiation of the Th cell subsets, Th17 and follicular helper T (TFH) cells. Because of its potent activity in both myeloid and lymphoid cell immune responses, it has been implicated in a number of autoimmune diseases and has also been used as a therapeutic agent in the treatment of some cancers. In this study, we demonstrate that c-Rel, a member of the NF-κB family of transcription factors, is required for IL-21 gene expression in T lymphocytes. IL-21 mRNA and protein levels are reduced in the CD4+ cells of rel−/− mice when compared with rel+/+ mice in both in vitro and in vivo models. A c-Rel binding site identified in the proximal promoter of il21 is confirmed to bind c-Rel in vitro and in vivo and to regulate expression from the il21 promoter in T cells. Downstream of IL-21 expression, Th17, TFH, and germinal center B cell development are also impaired in rel−/− mice. The administration of IL-21 protein rescued the development of TFH cells but not germinal center B cells. Taken together, c-Rel plays an important role in the expression of IL-21 in T cells and subsequently in IL-21-dependent TFH cell development

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