Dergi makalesi Açık Erişim

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

2019    Eken, Ahmet; Cansever, Murat; Somekh, Ido; Mizoguchi, Yoko; Zietara, Natalia; Okus, Fatma Zehra; Erdem, Serife; Canatan, Halit; Akyol, Sefika; Ozcan, Alper; Karakukcu, Musa; Hollizeck, Sebastian; Rohlfs, Meino; Unal, Ekrem; Klein, Christoph; Patiroglu, Turkan

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.