We have unraveled an instrumental role of TET proteins in the lineage specification, stability and immune function of various T cell subsets.

Simultaneous deletion of Tet2 and Tet3 impairs T cell homeostasis and results in iNKT cell expansion and disease. (a) Increased size of spleen in Tet2-3 DKO mice. (b) Disease emergence in Tet2-3 DKO mice. (c) Expansion of invariant iNKT cells in Tet2-3 DKO mice. (Tsagaratou et al, Nat Immunol. 2017 Jan;18(1):45-53.)

 

Gene Expression profiles of wild type and Tet2-Tet3 DKO iNKT cells. (a) Mean average (MA) plot of differentially expressed genes. (b) Differentially expressed Transcription factors, cytokines and receptors in wild type and Tet mutant iNKT cells. (c) Focus on selected genes that are differentially expressed during sequential stages of iNKT cell development when comparing Tet2-3 DKO iNKT cells to their wild type counterparts. (Tsagaratou et al, Nat Immunol. 2017 Jan;18(1):45-53.)

We will ask the role of each TET protein in maintaining proper T-cell function and protecting from the emergence of autoimmunity-inflammation.