Transcription factors controlling development and function of innate lymphoid cells

Int Immunol. 2014 Mar;26(3):119-28. doi: 10.1093/intimm/dxt063.


Innate lymphoid cells (ILCs) are a heterogeneous group of lymphocytes, which play an important role in tissue homeostasis at epithelial surfaces. They are scarce in spleen and lymph nodes, but substantial numbers can be found in the intestinal mucosa even at steady state. There, they represent the first line of defence against invading pathogens and contribute to lymphorganogenesis, tissue repair and, when inappropriately activated, immune pathology. Lineage-specific development, function and maintenance of these cells depend on a restricted set of transcription factors that partially emerged as a result of diversification and selection during vertebrate evolution. The differential expression of transcription factors regulates unique developmental programs, which endow the different ILC subsets with specific effector functions. Despite this division of labour, ILCs are considered to share a common origin, as they all are progeny of the common lymphoid progenitor, rely on the common γ-chain (γc) used by various cytokine receptors and show a developmental requirement for the transcriptional regulator Id2 (inhibitor of DNA binding 2). Here, we review the transcriptional programs required for the development and function of ILCs and give an overview of the evolution of transcription factors and cytokines expressed by ILCs.

Keywords: GATA-3; ILC; RORγt; T-bet; evolution; inflammation; lymphorganogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution
  • Cell Differentiation
  • Cell Lineage
  • Cytokines / metabolism
  • Gene Expression Regulation, Developmental / immunology
  • Homeostasis
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate / genetics
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Intestinal Mucosa / immunology*
  • Lymphocyte Activation / genetics
  • Lymphocytes / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*


  • Cytokines
  • Interleukin Receptor Common gamma Subunit
  • Transcription Factors