Genetic Deficiency and Biochemical Inhibition of ITK Affect Human Th17, Treg, and Innate Lymphoid Cells

Eken A. , Cansever M., Somekh I., Mizoguchi Y., Zietara N., Okus F., ...More

JOURNAL OF CLINICAL IMMUNOLOGY, vol.39, no.4, pp.391-400, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 4
  • Publication Date: 2019
  • Doi Number: 10.1007/s10875-019-00632-5
  • Page Numbers: pp.391-400
  • Keywords: ITK, Th17, Treg, Foxp3, ILC, interleukin-2-inducible T cell kinase, ibrutinib, TEC FAMILY KINASE, DELTA-T-CELLS, CUTTING EDGE, MICE LACKING, RECEPTOR, TH2, EBV, EXPRESSION, GAMMA, DEGRANULATION


Purpose Interleukin-2-inducible T cell kinase (ITK) is an important mediator of T cell receptor signaling. Loss of function mutations in ITK results in hypogammaglobulinemia and CD4+ T cell loss in humans, and the patients often present with EBV-associated B cell lymphoproliferative syndrome. Itk-deficient mice show loss of T cell naivety, impaired cytolytic activity of CD8+ T cells, and defects in CD4+ T cell lineage choice decisions. In mice, Itk mutations were shown to affect Th17-Treg lineage choice in favor of the latter. In this study, we explored whether human ITK reciprocally regulates Th17-Treg balance as its murine ortholog.