The transcription factor GATA3 is critical for the development of all IL-7Rα-expressing innate lymphoid cells

Immunity. 2014 Mar 20;40(3):378-88. doi: 10.1016/j.immuni.2014.01.012. Epub 2014 Mar 13.

Abstract

Innate lymphoid cells (ILCs) are critical in innate immune responses to pathogens and lymphoid organ development. Similar to CD4(+) T helper (Th) cell subsets, ILC subsets positive for interleukin-7 receptor α (IL-7Rα) produce distinct sets of effector cytokines. However, the molecular control of IL-7Rα(+) ILC development and maintenance is unclear. Here, we report that GATA3 was indispensable for the development of all IL-7Rα(+) ILC subsets and T cells but was not required for the development of classical natural killer cells. Conditionally Gata3-deficient mice had no lymph nodes and were susceptible to Citrobactor rodentium infection. After the ILCs had fully developed, GATA3 remained important for the maintenance and functions of ILC2s. Genome-wide gene expression analyses indicated that GATA3 regulated a similar set of cytokines and receptors in Th2 cells and ILC2s, but not in ILC3s. Thus, GATA3 plays parallel roles in regulating the development and functions of CD4(+) T cells and IL-7Rα(+) ILCs.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Citrobacter rodentium / immunology
  • Enterobacteriaceae Infections / genetics
  • Enterobacteriaceae Infections / immunology
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation*
  • Genetic Predisposition to Disease
  • Immunity, Innate / genetics*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism*
  • Mice
  • Mice, Knockout
  • Models, Immunological
  • Proto-Oncogene Proteins c-vav / genetics
  • Proto-Oncogene Proteins c-vav / metabolism
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / metabolism

Substances

  • GATA3 Transcription Factor
  • Proto-Oncogene Proteins c-vav
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain

Associated data

  • GEO/GSE47851