IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors

Naoko Satoh-Takayama, Sarah Lesjean-Pottier, Paulo Vieira, Shinichiro Sawa, Gerard Eberl, Christian A.J. Vosshenrich, James P. Di Santo

Research output: Contribution to journalArticlepeer-review

267 Citations (Scopus)


The natural cytotoxicity receptor NKp46 (encoded by Ncr1) was recently shown to identify a subset of noncytotoxic, Rag-independent gut lymphocytes that express the transcription factor Rorc, produce interleukin (IL)-22, and provide innate immune protection at the intestinal mucosa. Intestinal CD3 -NKp46+ cells are phenotypically heterogeneous, comprising a minority subset that resembles classical mature splenic natural killer (NK) cells (NK1.1+, Ly49+) but also a large CD127 +NK1.1- subset of lymphoid tissue inducer (LTi)-like Rorc+ cells that has been proposed to include NK cell precursors. We investigated the developmental relationships between these intestinal CD3 -NKp46+ subsets. Gut CD3-NKp46+ cells were related to LTi and NK cells in requiring the transcriptional inhibitor Id2 for normal development. Overexpression of IL-15 in intestinal epithelial cells expanded NK1.1+ cells within the gut but had no effect on absolute numbers of the CD127+NK1.1-Rorc+ subset of CD3-NKp46+ cells. In contrast, IL-7 deficiency strongly reduced the overall numbers of CD3-NKp46+NK1. 1- cells that express Rorc and produce IL-22 but failed to restrict homeostasis of classical intestinal NK1.1+ cells. Finally, in vivo fate-mapping experiments demonstrated that intestinal NK1.1 +CD127- cells are not the progeny of Rorc-expressing progenitors, indicating that CD127+NK1.1-Rorc+ cells are not canonical NK cell precursors. These studies highlight the independent cytokine regulation of functionally diverse intestinal NKp46 + cell subsets.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalJournal of Experimental Medicine
Issue number2
Publication statusPublished - Feb 15 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine


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