Hu & Zhang Lab
The State Key Laboratory of Biotherapy Si-Chuan University

TOX controls the development of innate lymphoid cells

Innate lymphoidcells (ILCs) develop from common lymphoid progenitors. Several transcriptionalfactors have been reported as critical regulators in the ILC development, suchas Id2, NFIL3 etc. Recently, Seehus et al reported another TF TOX as a key factor in early ILC development.

TOX, aka thymocyteselection–associated high-mobility-group protein, is firstly discoveredupregulated in CD4+CD8+ T cell, indicating its pivotal role in T celldevelopment in thymus. In their paper, they showed TOX-KO mice have defectedall subpopulation of ILC, including ILC1, ILC2 and ILC3, as well as NK cellsand LTi cell, suggesting the function of TOX in the early development of ILC.Transcriptome assay revealed TOX KO precursors lack many key transcriptionfactors such as GATA-3, RORa, RORgt and PLZF. The authors also generated a TOX reporter mouse ToxTOM and crossed with Id2GFP reporter mouse, to study the whenTOX functions in ILC development. Their data suggested that (Lin)CD127+CD25TOXId2α4β7+ cells are the common precursor of NK cells and other ILCs that,in the absence of TOX, is unable to differentiate into CHILPs and thus into LTicells and ILC subpopulations. Comparative transcriptome analysis of bone marrow progenitorsrevealed that TOX-deficient cells failed to upregulate many genes of the ILCprogram, including genes that are targets of Notch, which indicated that TOX isa key determinant of early specification to the ILC lineage.

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