Notch signaling is necessary for adult, but not fetal, development of RORγt(+) innate lymphoid cells

Nat Immunol. 2011 Sep 11;12(10):949-58. doi: 10.1038/ni.2105.

Abstract

The transcription factor RORγt is required for the development of several innate lymphoid populations, such as lymphoid tissue-inducer cells (LTi cells) and cells that secrete interleukin 17 (IL-17) or IL-22. The progenitor cells as well as the developmental stages that lead to the emergence of RORγt(+) innate lymphoid cells (ILCs) remain undefined. Here we identify the chemokine receptor CXCR6 as an additional marker of the development of ILCs and show that common lymphoid progenitors lost B cell and T cell potential as they successively acquired expression of the integrin α(4)β(7) and CXCR6. Whereas fetal RORγt(+) cells matured in the fetal liver environment, adult bone marrow-derived RORγt(+) ILCs matured outside the bone marrow, in a Notch2-dependent manner. Therefore, fetal and adult environments influence the differentiation of RORγt(+) cells differently.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • DNA-Binding Proteins / physiology
  • Fetus / immunology*
  • Immunity, Innate
  • Integrins / physiology
  • Lymphocytes / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / physiology*
  • Receptor, Notch2 / physiology*
  • Receptors, CXCR / physiology
  • Receptors, CXCR6
  • Signal Transduction*

Substances

  • Cxcr6 protein, mouse
  • DNA-Binding Proteins
  • Integrins
  • Notch2 protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rag2 protein, mouse
  • Receptor, Notch2
  • Receptors, CXCR
  • Receptors, CXCR6
  • integrin alpha4beta7