Allele‐sensitive mutant, Itk as , reveals that Itk kinase activity is required for Th1, Th2, Th17, and i NKT‐cell cytokine production

• Published in: European journal of immunology 2015-08, Vol.45 (8), p.2276-2285
• Main Authors: Kannan, Arun, Lee, YongChan, Qi, Qian, Huang, Weishan, Jeong, Ah‐Reum, Ohnigian, Sarah, August, Avery
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201445087

Itk −/− mice exhibit defects in the activation, development, and function of CD4 + and CD8 + T cells and i NKT 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 (Itk as ) whose catalytic activity can be selectively inhibited by analogs of the PP1 kinase inhibitor. We show that Itk as behaves like WT Itk in the absence of the inhibitor and can rescue the development of Itk −/− T cells in mice. Using mice carrying Itk as , we show using its inhibitor that Itk activity is required not only for Th2, Th17, and i NKT‐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 i NKT cells, Th1, Th2, and Th17 cells.