The many roles of TOX in the immune system

TOX is a member of an evolutionarily conserved DNA-binding protein family and is expressed in several immune-relevant cell subsets. Here, we review the key role of TOX in regulating development of CD4 T cells, natural killer cells and lymphoid tissue inducer cells, the latter responsible for the generation of lymph nodes. Although the exact molecular mechanism of action of TOX remains to be elucidated, the role of TOX in establishment of gene programs in the thymus and the potential of TOX as a regulator of E protein activity are discussed.

► The TOX protein is a member of a small subfamily of HMG-box DNA binding proteins.
► The TOX protein is predicted to interact with DNA in a sequence-independent fashion.
► TOX is required for CD4 T cell lineage development in the thymus.
► TOX regulates NK cell development in the bone marrow and lymph node organogenesis.