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Innate lymphoid cell development requires TOX-dependent generation of a common ILC progenitor

ABSTRACT: Subtypes of innate lymphoid cells (ILC), defined by effector function and transcription factor expression, have recently been identified. In the adult, ILC derive from common lymphoid progenitors in bone marrow, although transcriptional regulation of the developmental pathways involved remains poorly defined. TOX is required for development of lymphoid tissue inducer cells, a type of ILC3 required for lymph node organogenesis, and NK cells, a type of ILC1. We show here that production of multiple ILC lineages requires TOX, as a result of TOX-dependent development of common ILC progenitors. Comparative transcriptome analysis demonstrated failure to induce various aspects of the ILC gene program in the absence of TOX, implicating this nuclear factor as a key early determinant of ILC lineage specification. TOX KO vs. wild tyype

ORGANISM(S): Mus musculus  

SUBMITTER: Brian de la Torre   Vincent Funari  Iliyan Iliev  Parinaz Aliahmad  Jonathan Kaye  Corey Seehus  Lindsay Spurka  Wolf Wiedemeyer 

PROVIDER: E-GEOD-65850 | ArrayExpress | 2015-04-27



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

Seehus Corey R CR   Aliahmad Parinaz P   de la Torre Brian B   Iliev Iliyan D ID   Spurka Lindsay L   Funari Vincent A VA   Kaye Jonathan J  

Nature immunology 20150427 6

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  ...[more]

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