Suppression of Th17 differentiation by IEX-1

In fighting various invaders, naïve T cells differentiate into distinct T-cell subsets, including Th1, Th2, Th17, and T regulatory (Treg) cells, which must be delicately balanced so that the invader can be sufficiently eliminated, while causing no harm to our body.  IEX-1 can be rapidly induced in T cells following activation and protects them from apoptosis by modulating the production of reactive oxygen species (ROS) in mitochondria. 

Mice with targeted IEX-1 expression to lymphocytes develop a lupus-like autoimmune disease and T cell lymphoma due to insufficient apoptosis of Th1-like cells.  Consistent with a role for IEX-1 in a T cell subset-specific manner, null mutation of IEX-1 renders CD4+ T cells an intrinsic tendency to differentiate into Th17 cells relative to wild type (WT) CD4+ T cells.  These observations argue a vital role for IEX-1 in regulation of the survival and/or differentiation of one T cell subset over the other. 

Thus, its dysregulation, irrespective of overexpression or deletion both causes an imbalance in immune responses, and thus immune disorders.