Cell
Volume 157, Issue 2, 10 April 2014, Pages 340-356
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Article
Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages

https://doi.org/10.1016/j.cell.2014.03.030Get rights and content
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Highlights

  • An Id2-expressing common progenitor to all IL-7Rα+ helper-like ILC lineages, ChILP

  • Identification of an intestinal mucosa-resident, T-bet-dependent, non-NK ILC1 subset

  • IL-7Rα+ ILC1s require IL-15, but not IL-7 receptor signaling for maintenance

  • ILC1s provide innate protection against intracellular infections

Summary

Innate lymphoid cells (ILCs) are a recently recognized group of lymphocytes that have important functions in protecting epithelial barriers against infections and in maintaining organ homeostasis. ILCs have been categorized into three distinct groups, transcriptional circuitry and effector functions of which strikingly resemble the various T helper cell subsets. Here, we identify a common, Id2-expressing progenitor to all interleukin 7 receptor-expressing, “helper-like” ILC lineages, the CHILP. Interestingly, the CHILP differentiated into ILC2 and ILC3 lineages, but not into conventional natural killer (cNK) cells that have been considered an ILC1 subset. Instead, the CHILP gave rise to a peculiar NKp46+ IL-7Rα+ ILC lineage that required T-bet for specification and was distinct of cNK cells or other ILC lineages. Such ILC1s coproduced high levels of IFN-γ and TNF and protected against infections with the intracellular parasite Toxoplasma gondii. Our data significantly advance our understanding of ILC differentiation and presents evidence for a new ILC lineage that protects barrier surfaces against intracellular infections.

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11

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12

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