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 journalArticlepeer-review

62 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2010
Externally publishedYes


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