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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Roy, S; Moore, AJ; Love, C; Reddy, A; Rajagopalan, D; Dave, SS; Li, L; Murre, C; Zhuang, Y

Published Date

  • 2018

Published In

Volume / Issue

  • 9 /

Start / End Page

  • 42 -

PubMed ID

  • 29416542

Pubmed Central ID

  • 29416542

International Standard Serial Number (ISSN)

  • 1664-3224

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2018.00042

Language

  • eng

Conference Location

  • Switzerland