TY - JOUR
T1 - Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production
AU - Kannan, Arun
AU - Lee, Yongchan
AU - Qi, Qian
AU - Huang, Weishan
AU - Jeong, Ah Reum
AU - Ohnigian, Sarah
AU - August, Avery
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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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U2 - 10.1002/eji.201445087
DO - 10.1002/eji.201445087
M3 - Article
C2 - 25989458
AN - SCOPUS:84938975766
SN - 0014-2980
VL - 45
SP - 2276
EP - 2285
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 8
ER -