Shared dependence on TOX for development of lymphoid tissue inducer cell and NK cell lineages

Thymocyte selection-associated HMG box factor (TOX) is a DNA-binding factor required for development of CD4 T cells, natural killer T cells, and T regulatory cells. Here we document that both NK cell development and lymphoid tissue organogenesis are inhibited in the absence of TOX. We find that development of lymphoid tissue inducer cells, a rare subset of specialized cells that plays an integral role in lymphoid tissue organogenesis, requires TOX. Tox is highly upregulated in immature NK cells in the bone marrow, consistent with the loss of mature NK cells in the absence of this nuclear protein. Thus, multiple cell lineages in the immune system share a TOX-dependent step for development.