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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 4
  • Publication Date: 2019
  • Doi Number: 10.1007/s10875-019-00632-5
  • Journal Name: JOURNAL OF CLINICAL IMMUNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • 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
  • Erciyes University Affiliated: Yes

Abstract

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.