The Role of TOX in the Development of Innate Lymphoid Cells

Figure 2

Proposed model of the role of TOX in innate lymphoid cell development. We propose that cells represent a CLP to CHILP transitional cell population that requires TOX for progression. Notch signaling in CLP may initiate ILC differentiation but is terminated upon downregulation of Notch at the transitional stage, and TOX could influence regulation of Notch gene targets. The NK cell lineage originates from a pre-CHILP stage (EILP), possibly via the αLP progenitor that is also TOX dependent. In the absence of TOX, rNKp cells fail to develop, but a population of Lin⁻CD122⁺ cells of unknown origin or function remains. Development of tissue resident NK cells is less affected by loss of TOX than are cNK cells, possibly indicative of a distinct pathway of development. Similarly, ILC3s are found in the gut of TOX-deficient mice, but whether this is due to a TOX-independent pathway of development or homeostatic proliferation is not clear.