Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation

Sean Diehl, Chi Wing Chow, Linda Weiss, Alois Palmetshofer, Thomas Twardzik, Laura Rounds, Edgar Serfling, Roger J. Davis, Juan Anguita, Mercedes Rincón

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Interleukin (IL)-6 is produced by professional antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells. It has been previously shown that APC-derived IL-6 promotes the differentiation of naive CD4+ T cells into effector T helper type 2 (Th2) cells. Here, we have studied the molecular mechanism for IL-6-mediated Th2 differentiation. During the activation of CD4+ T cells, IL-6 induces the production of IL-4, which promotes the differentiation of these cells into effector Th2 cells. Regulation of IL-4 gene expression by IL-6 is mediated by nuclear factor of activated T cells (NFAT), as inhibition of NFAT prevents IL-6-driven IL-4 production and Th2 differentiation. IL-6 upregulates NFAT transcriptional activity by increasing the levels of NFATc2. The ability of IL-6 to promote Th2 differentiation is impaired in CD4+ T cells that lack NFATc2, demonstrating that NFATc2 is required for regulation of IL-4 gene expression by IL-6. Regulation of NFATc2 expression and NFAT transcriptional activity represents a novel pathway by which IL-6 can modulate gene expression.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalJournal of Experimental Medicine
Volume196
Issue number1
DOIs
StatePublished - Jul 1 2002
Externally publishedYes

Fingerprint

Interleukin-6
NFATC Transcription Factors
Interleukin-4
Th2 Cells
Antigen-Presenting Cells
T-Lymphocytes
Gene Expression
CCAAT-Enhancer-Binding Protein-beta
Dendritic Cells
Cell Differentiation
B-Lymphocytes
Up-Regulation
Macrophages

Keywords

  • CD4 T cells
  • Cytokines
  • Gene regulation
  • IL-4
  • NFAT

ASJC Scopus subject areas

  • Immunology

Cite this

Diehl, S., Chow, C. W., Weiss, L., Palmetshofer, A., Twardzik, T., Rounds, L., ... Rincón, M. (2002). Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. Journal of Experimental Medicine, 196(1), 39-49. https://doi.org/10.1084/jem.20020026

Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. / Diehl, Sean; Chow, Chi Wing; Weiss, Linda; Palmetshofer, Alois; Twardzik, Thomas; Rounds, Laura; Serfling, Edgar; Davis, Roger J.; Anguita, Juan; Rincón, Mercedes.

In: Journal of Experimental Medicine, Vol. 196, No. 1, 01.07.2002, p. 39-49.

Research output: Contribution to journalArticle

Diehl, S, Chow, CW, Weiss, L, Palmetshofer, A, Twardzik, T, Rounds, L, Serfling, E, Davis, RJ, Anguita, J & Rincón, M 2002, 'Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation', Journal of Experimental Medicine, vol. 196, no. 1, pp. 39-49. https://doi.org/10.1084/jem.20020026
Diehl, Sean ; Chow, Chi Wing ; Weiss, Linda ; Palmetshofer, Alois ; Twardzik, Thomas ; Rounds, Laura ; Serfling, Edgar ; Davis, Roger J. ; Anguita, Juan ; Rincón, Mercedes. / Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 1. pp. 39-49.
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