Ekrem Unal, Turkey
Erciyes Universty, Faculty of Medicine Pediatric Hematology-OncologyPresenter of 1 Presentation
CHARACTERIZATION OF HELPER CD4+ T CELL SUBSETS IN PATIENTS WITH TAOK2 MUTATIONS
Abstract
Background and Aims
Thousand and one amino-acid kinase 2 (TAOK2), is a transmembrane protein which belongs to mammalian sterile 20 (STE20)-like kinase family To this day, only one report documented that TAOK2 might regulate T cell proliferation. Whether TAOK2 has any role in CD4+ T cell subset generation or cytokine secretion has not been assessed. In this study we aimed to characterize helper T cell signature cytokines and innate lymphoid cells in three patients with two novel TAOK2 mutations.
Methods
After whole exome sequencing mutations were confirmed by Sanger sequencing. Peripheral blood mononuclear cells (PBMCs) were isolated via Ficoll-Paque and stimulated with phorbol myristate acetate/Ionomycin or CD3/28. IL-17, IL-22, GM-CSF, IFN-γ production by T cells were assessed by intracellular cytokine staining. T cell proliferation, apoptosis was quantified by flow cytometry. IL-6, IL-12 induced STAT3 and STAT4 phosphorylation was tested by phospho-flow based assay. Innate lymphoid cell frequency was measured by flow cytometry.
Results
Patient-1 has presented with severe invasive fungal infection and had TAOK2 (NM_016151.3: c.3259C>T, p.Arg1087Trp) mutation. The T cells of this patient were hyperproliferative to CD3/CD28 stimulation, showed reduced IL-17, IL-4 and IFN-γ production. IL-1B-induced ERK1/2 phosphorylation was defective but, STAT3 phosphorylation was augmented in patient PBMCs. Patient 2 and 3, which were siblings (with rhabdomyosarcoma, and osteosarcoma, respectively) had TAOK2 (NM_016151.3: c.1324C>T, p.Pro442Ser) mutation. Their T cells showed reduced IL-4 and IFN-γ. Patient one had reduced ILC3 subset, while patient 2 and 3 had normal ILC levels.
Conclusions
Our results reveal unique and common consequences of two distinct variants of TAOK2 on immune cells.