IS ZEB2 involved in lineage commitment of the human Th1/17 subset, and why does FOXP3 repress it in Treg? (#159)
ZEB2 has a well established role in promoting cancer metastasis in a number of different cancer types. A more complex role for ZEB2 is now emerging in both the innate and adaptive compartments of the immune system. ZEB2 promotes maturation of cells in both the CD4 and CD8 T cell compartments as well as cells of the B cell compartment. ZEB2 similarly promotes maturation of cells of the innate arm of the immune system. We have evidence that ZEB2 is restrained in human T regulatory cells by FOXP3 and FOXP3 induced miR-155. Loss of FOXP3 and miR-155 relieves this restraint. We provide new evidence to suggest a role for ZEB2 in lineage programming of human CD4 T cells. Using a chemokine receptor based phenotyping panel to segregate T cell subsets, combined with lentiviral expression of ZEB2 in both Treg and T conventional cells, our preliminary data suggests that ZEB2 may be linked to the commitment of both Treg and T conventional cells into a Th1/ Th17 lineage. Alterations in the regulation of ZEB2 in the CD4 compartment may result in skewing of the proportions of specific T cell subsets, resulting in immune imbalance. This has important implications for the clinical setting as elevated Th1/Th17 T cell subsets have well documented roles in several autoimmune disease phenotypes including multiple sclerosis, IBD and Type 1 diabetes.