Transcriptional regulation of innate and adaptive lymphocyte lineages

Annu Rev Immunol. 2015;33:607-42. doi: 10.1146/annurev-immunol-032414-112032. Epub 2015 Feb 4.


The lymphocyte family has expanded significantly in recent years to include not only the adaptive lymphocytes (T cells, B cells) and NK cells, but also several additional innate lymphoid cell (ILC) types. ILCs lack clonally distributed antigen receptors characteristic of adaptive lymphocytes and instead respond exclusively to signaling via germline-encoded receptors. ILCs resemble T cells more closely than any other leukocyte lineage at the transcriptome level and express many elements of the core T cell transcriptional program, including Notch, Gata3, Tcf7, and Bcl11b. We present our current understanding of the shared and distinct transcriptional regulatory mechanisms involved in the development of adaptive T lymphocytes and closely related ILCs. We discuss the possibility that a core set of transcriptional regulators common to ILCs and T cells establish enhancers that enable implementation of closely aligned effector pathways. Studies of the transcriptional regulation of lymphopoiesis will support the development of novel therapeutic approaches to correct early lymphoid developmental defects and aberrant lymphocyte function.

Keywords: T cell development; enhancer regulation; evolution of lymphocytes; innate lymphoid cell development; lineage commitment; transcription factors.

Publication types

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

MeSH terms

  • Adaptive Immunity / genetics*
  • Animals
  • Cell Differentiation
  • Cell Lineage / genetics*
  • Gene Expression Regulation*
  • Humans
  • Immunity, Innate / genetics*
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Transcription, Genetic*