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The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.

TitleThe development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.
Publication TypeJournal Article
Year of Publication2015
AuthorsSeehus CR, Aliahmad P, de la Torre B, Iliev ID, Spurka L, Funari VA, Kaye J
JournalNat Immunol
Volume16
Issue6
Pagination599-608
Date Published2015 Jun
ISSN1529-2916
KeywordsAnimals, Bone Marrow Cells, Cell Differentiation, Cell Lineage, Cell Proliferation, Cell Survival, Cells, Cultured, Female, Homeodomain Proteins, Immunity, Innate, Killer Cells, Natural, Lymphocyte Subsets, Lymphoid Progenitor Cells, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, Notch, Transcriptome
Abstract

Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.

DOI10.1038/ni.3168
Alternate JournalNat. Immunol.
PubMed ID25915732
PubMed Central IDPMC4439271
Grant List5R01AI054977 / AI / NIAID NIH HHS / United States
DK098310 / DK / NIDDK NIH HHS / United States
HHSN272201300006C / / PHS HHS / United States
K99 DK098310 / DK / NIDDK NIH HHS / United States
R01 AI054977 / AI / NIAID NIH HHS / United States