The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development

J Exp Med. 2015 Jun 1;212(6):865-74. doi: 10.1084/jem.20142318. Epub 2015 May 11.

Abstract

Group 2 innate lymphoid cells (ILCs), or ILC2s, are a subset of recently identified ILCs, which play important roles in innate immunity by producing type 2 effector cytokines. Several transcription factors have been found to have critical functions in the development of both ILC2s and T cells. We report here that Bcl11b, a transcription factor essential in T cell lineage commitment and maintenance, is specifically expressed in progenitors committed to the ILC2 lineage and is required for ILC2 development. The Bcl11b gene is expressed in ∼28% of ILC progenitors (ILCPs; common helper innate lymphoid progenitors or ILCPs expressing either ID2 or promyelocytic leukemia zinc finger, respectively). Both in vitro and in vivo, these Bcl11b-expressing early ILCPs generate only ILC2s. Inactivation of Bcl11b causes a complete loss of ILC2 development from hematopoietic progenitors, which is confirmed upon immune challenge with either papain administration or influenza virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Cell Separation
  • Chromatin Immunoprecipitation
  • Female
  • Flow Cytometry
  • GATA3 Transcription Factor / metabolism
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genes, Reporter
  • Hematopoietic Stem Cells / cytology
  • Immunity, Innate
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Interleukin-1 Receptor-Like 1 Protein
  • Lymphocytes / cytology*
  • Lymphocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Interleukin / metabolism
  • Repressor Proteins / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Zinc Fingers

Substances

  • Bcl11b protein, mouse
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Icos protein, mouse
  • Il1rl1 protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-1 Receptor-Like 1 Protein
  • Receptors, Interleukin
  • Repressor Proteins
  • Tumor Suppressor Proteins