Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt- lymphoid cells

EMBO J. 2011 Jun 17;30(14):2934-47. doi: 10.1038/emboj.2011.201.

Abstract

The gut is a major barrier against microbes and encloses various innate lymphoid cells (ILCs), including two subsets expressing the natural cytotoxicity receptor NKp46. A subset of NKp46(+) cells expresses retinoic acid receptor-related orphan receptor γt (RORγt) and produces IL-22, like lymphoid tissue inducer (LTi) cells. Other NKp46(+) cells lack RORγt and produce IFN-γ, like conventional Natural Killer (cNK) cells. The identity, the regulation and the in vivo functions of gut NKp46(+) ILCs largely remain to be unravelled. Using pan-genomic profiling, we showed here that small intestine (SI) NKp46(+)RORγt(-) ILCs correspond to SI NK cells. Conversely, we identified a transcriptional programme conserved in fetal LTi cells and adult SI NKp46(+)RORγt(+) and NKp46(-)RORγt(+) ILCs. We also demonstrated that the IL-1β/IL-1R1/MyD88 pathway, but not the commensal flora, drove IL-22 production by NKp46(+)RORγt(+) ILCs. Finally, oral Listeria monocytogenes infection induced IFN-γ production in SI NK and IL-22 production in NKp46(+)RORγt(+) ILCs, but only IFN-γ contributed to control bacteria dissemination. NKp46(+) ILC heterogeneity is thus associated with subset-specific transcriptional programmes and effector functions that govern their implication in gut innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage*
  • Female
  • Flow Cytometry
  • Immunity, Innate*
  • Intestine, Small / immunology
  • Intestine, Small / metabolism
  • Intestine, Small / microbiology
  • Listeria monocytogenes / isolation & purification
  • Listeriosis / metabolism
  • Listeriosis / microbiology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Lymphocytes / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / physiology
  • Natural Cytotoxicity Triggering Receptor 1 / genetics
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism*
  • Receptors, Interleukin-1 / physiology
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Retinoic Acid Receptor gamma
  • Tissue Distribution

Substances

  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Natural Cytotoxicity Triggering Receptor 1
  • Receptors, Interleukin-1
  • Receptors, Retinoic Acid