Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection

Front Immunol. 2018 Jan 24:9:42. doi: 10.3389/fimmu.2018.00042. eCollection 2018.

Abstract

A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function. There is also biased rearrangement in Id-deficient DP cells that promotes selection into the iNKT lineage in these mice. The observed expansion of iNKT cells is not abrogated by blocking pre-TCR signaling, which is required for conventional αβ T cell development. Finally, E2A is found to be a key transcriptional regulator of both iNKT and γδNKT lineages, which appear to have shared lineage history. Therefore, our study reveals a previously unappreciated role of E2A in coordinating the development of the iNKT lineage at an early stage, prior to their TCR-mediated selection alongside conventional αβ T cells.

Keywords: E2A; Id proteins; innate lymphocytes; natural killer T cells; thymus.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Differentiation
  • Inhibitor of Differentiation Proteins / physiology*
  • Mice, Knockout
  • Natural Killer T-Cells / physiology*
  • Receptors, Antigen, T-Cell / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Inhibitor of Differentiation Proteins
  • Receptors, Antigen, T-Cell
  • Tcf3 protein, mouse