Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production

Arun Kannan, Yongchan Lee, Qian Qi, Weishan Huang, Ah Reum Jeong, Sarah Ohnigian, Avery August

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Itk-/- mice exhibit defects in the activation, development, and function of CD4+ and CD8+ T cells and iNKT cells. These and other defects in these mice make it difficult to uncouple the developmental versus functional requirement of Itk signaling. Here, we report an allele-sensitive mutant of Itk (Itkas) whose catalytic activity can be selectively inhibited by analogs of the PP1 kinase inhibitor. We show that Itkas behaves like WT Itk in the absence of the inhibitor and can rescue the development of Itk-/- T cells in mice. Using mice carrying Itkas, we show using its inhibitor that Itk activity is required not only for Th2, Th17, and iNKT-cell cytokine production, but also surprisingly, for Th1 cytokine production. This work has important implications for understanding the role of Itk signaling in the development versus function of iNKT cells, Th1, Th2, and Th17 cells.

Original languageEnglish (US)
Pages (from-to)2276-2285
Number of pages10
JournalEuropean Journal of Immunology
Volume45
Issue number8
DOIs
StatePublished - Aug 1 2015

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Th17 Cells
Natural Killer T-Cells
Phosphotransferases
Alleles
Cytokines
T-Lymphocytes
Th2 Cells
Th1 Cells

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kannan, Arun ; Lee, Yongchan ; Qi, Qian ; Huang, Weishan ; Jeong, Ah Reum ; Ohnigian, Sarah ; August, Avery. / Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production. In: European Journal of Immunology. 2015 ; Vol. 45, No. 8. pp. 2276-2285.
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abstract = "Itk-/- mice exhibit defects in the activation, development, and function of CD4+ and CD8+ T cells and iNKT cells. These and other defects in these mice make it difficult to uncouple the developmental versus functional requirement of Itk signaling. Here, we report an allele-sensitive mutant of Itk (Itkas) whose catalytic activity can be selectively inhibited by analogs of the PP1 kinase inhibitor. We show that Itkas behaves like WT Itk in the absence of the inhibitor and can rescue the development of Itk-/- T cells in mice. Using mice carrying Itkas, we show using its inhibitor that Itk activity is required not only for Th2, Th17, and iNKT-cell cytokine production, but also surprisingly, for Th1 cytokine production. This work has important implications for understanding the role of Itk signaling in the development versus function of iNKT cells, Th1, Th2, and Th17 cells.",
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Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production. / Kannan, Arun; Lee, Yongchan; Qi, Qian; Huang, Weishan; Jeong, Ah Reum; Ohnigian, Sarah; August, Avery.

In: European Journal of Immunology, Vol. 45, No. 8, 01.08.2015, p. 2276-2285.

Research output: Contribution to journalArticle

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