T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype

Anubhav N. Mathur, Hua Chen Chang, Dimitrios G. Zisoulis, Reuben Kapur, Maria Laura Belladonna, Geoffrey S. Kansas, Mark Kaplan

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

IL-23, an IL-12-related cytokine, induces an IL-17-secreting T-helper phenotype that is involved in autoimmune diseases and host defense against certain pathogens. Although the transcription factors required for development of IL-23-stimulated cells are unknown, we show that T-bet is a critical negative regulator of the IL-23-primed T-cell phenotype, which we term Th1β. Th1 or Th1β Tbx21-/- cultures secrete higher than WT levels of IL-17 in response to T-cell receptor (TCR) or IL-23 + IL-18 stimulation. Ectopic T-bet expression in Th1β cells promotes IFN-γ secretion but decreases IL-17 production. Although antigen-receptor stimulation of Th1β cells stimulates IL-17 production, it also induces the IFN-γ-independent expression of T-bet and progression to a Th1 cytokine secretion pattern. T-bet is required for the progression to the Th1 phenotype, because Tbx21 -/- Th1β cultures maintain the IL-17-secreting phenotype after 2 weeks of culture. Addition of IFN-γ to Tbx21-/- Th1β cultures cannot recover the progression to the Th1 phenotype, suggesting T-bet, rather than IFN-γ, mediates Th1β to Th1 progression. The transient nature of the Th1β phenotype suggests that these cells are a component of type I immunity and that T-bet expression is a critical determinant of Th1 versus Th1β cell fate.

Original languageEnglish
Pages (from-to)1595-1601
Number of pages7
JournalBlood
Volume108
Issue number5
DOIs
StatePublished - Sep 1 2006

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Interleukin-17
Interleukin-23
Phenotype
Th1 Cells
Cytokines
Antigen Receptors
Interleukin-18
T-cells
Pathogens
Interleukin-12
T-Cell Antigen Receptor
Cellular Structures
Transcription Factors
Autoimmune Diseases
Immunity
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. / Mathur, Anubhav N.; Chang, Hua Chen; Zisoulis, Dimitrios G.; Kapur, Reuben; Belladonna, Maria Laura; Kansas, Geoffrey S.; Kaplan, Mark.

In: Blood, Vol. 108, No. 5, 01.09.2006, p. 1595-1601.

Research output: Contribution to journalArticle

Mathur, Anubhav N. ; Chang, Hua Chen ; Zisoulis, Dimitrios G. ; Kapur, Reuben ; Belladonna, Maria Laura ; Kansas, Geoffrey S. ; Kaplan, Mark. / T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. In: Blood. 2006 ; Vol. 108, No. 5. pp. 1595-1601.
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