Interleukin-2-inducible T Cell Kinase (Itk) Network Edge Dependence for the Maturation of iNKT Cell

Qi, Qian; Xia, Mingcan; Bai, Y.; Yu, Sanhong; Cantorna, Margherita T.; August, Avery

doi:10.1074/jbc.m110.148205

Cited by 14 publications

(25 citation statements)

References 47 publications

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“…Itk has also been demonstrated to regulate IL-17A production in Th17 cells in vitro and in vivo via regulation of NFATc1 (21). In addition, in the absence of Itk, cytokine production by iNKT cells is significantly reduced (5,16,17). Two recent studies have also found that the increased IL-4 producing NKT-like Vg1.1/Vd6.2/3 gd T cells in Itk null mice contribute to the elevated serum IgE level in these mice (18,19).…”

Section: Introductionmentioning

confidence: 89%

“…These data suggest that Itk regulates the activation of SRF in a kinaseindependent manner, in part, via regulation of the ERK/ MAPK pathway. More interestingly, transgenic mice that express a kinase-dead mutant of Itk in T cells on Itk knockout background have a partial rescue of iNKT cell maturation (17). Expression of the kinase-dead mutant of Itk restored the expression of CD122 and transcription factors T-bet and eomesodermin in developing iNKT cells (17).…”

Section: Activation Of Itk Downstream Of the T Cell Receptormentioning

confidence: 98%

“…More interestingly, transgenic mice that express a kinase-dead mutant of Itk in T cells on Itk knockout background have a partial rescue of iNKT cell maturation (17). Expression of the kinase-dead mutant of Itk restored the expression of CD122 and transcription factors T-bet and eomesodermin in developing iNKT cells (17). In contrast, this kinase-dead Itk mutant does not rescue the function and frequency of iNKT cells, suggesting that the kinase activity of Itk is required for the function and frequency of iNKT cells (17).…”

Section: Activation Of Itk Downstream Of the T Cell Receptormentioning

confidence: 98%

“…Itk is also required for the development of conventional or naïve phenotype (CD44 low ) CD8 q and CD4 q T cells, but not for the development of innate or memory phenotype (CD44 hi ) CD8 q and CD4 q T cells (11)(12)(13)(14)(15). Besides conventional T cells, Itk has been shown to regulate the development of innate-like T cell populations, such as invariant NKT cells and NKT-like Vg1.1/Vd6.2/3 gd T cells (5,(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 98%

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Structure and function of Tec family kinase Itk

Kannan

August

2011

BioMolecular Concepts

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Itk is a member of the Tec family of kinases that is expressed predominantly in T cells. Itk regulates the T cell receptor signaling pathway to modulate T cell development and T helper cell differentiation, particularly Th2 differentiation. Itk is also important for the development and function of iNKT cells. In this review we discuss current progress on our understanding of the structure, activation and signaling pathway of Itk, in addition to inhibitors that have been developed, which target this kinase. We also place in context the function of Itk, available inhibitors and potential use in treating disease.

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Section: Introductionmentioning

confidence: 89%

Section: Activation Of Itk Downstream Of the T Cell Receptormentioning

confidence: 98%

Section: Activation Of Itk Downstream Of the T Cell Receptormentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Structure and function of Tec family kinase Itk

Kannan

August

2011

BioMolecular Concepts

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“…Grasis, J.A. et al, 2003;Iyer, A.S. & August, A., 2008;Qi, Q. et al, 2011). ITK mutations lead to fatal EBV induced lymphoproliferative disease characterized as hemophagocytic lymphohistiocytosis (HLH) and HL (Huck, K. et al, 2009;Stepensky, P. et al, 2011).…”

Section: Sh2d1amentioning

confidence: 99%

Recent Insights into the Biology of Hodgkin's Lymphoma

Banerjee¹

2012

Hodgkin's Lymphoma

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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

Lee

et al. 2015

Eur J Immunol

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Itk−/− mice exhibit defects in 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 this mutant, we show 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 development vs. function of iNKT cells, Th1, Th2 and Th17.

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Interleukin-2-inducible T Cell Kinase (Itk) Network Edge Dependence for the Maturation of iNKT Cell

Cited by 14 publications

References 47 publications

Structure and function of Tec family kinase Itk

Structure and function of Tec family kinase Itk

Recent Insights into the Biology of Hodgkin's Lymphoma

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

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