Essential functions for ID proteins at multiple checkpoints in invariant NKT cell development

J Immunol. 2013 Dec 15;191(12):5973-83. doi: 10.4049/jimmunol.1301521. Epub 2013 Nov 15.

Abstract

Invariant NKT (iNKT) cells display characteristics of both adaptive and innate lymphoid cells (ILCs). Like other ILCs, iNKT cells constitutively express ID proteins, which antagonize the E protein transcription factors that are essential for adaptive lymphocyte development. However, unlike ILCs, ID2 is not essential for thymic iNKT cell development. In this study, we demonstrated that ID2 and ID3 redundantly promoted iNKT cell lineage specification involving the induction of the signature transcription factor PLZF and that ID3 was critical for development of TBET-dependent NKT1 cells. In contrast, both ID2 and ID3 limited iNKT cell numbers by enforcing the postselection checkpoint in conventional thymocytes. Therefore, iNKT cells show both adaptive and innate-like requirements for ID proteins at distinct checkpoints during iNKT cell development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Cells, Cultured
  • Clonal Selection, Antigen-Mediated*
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Immunoglobulin Joining Region / genetics
  • Immunoglobulin Variable Region / genetics
  • Inhibitor of Differentiation Protein 2 / genetics
  • Inhibitor of Differentiation Protein 2 / physiology*
  • Inhibitor of Differentiation Proteins / deficiency
  • Inhibitor of Differentiation Proteins / physiology*
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / genetics
  • Lymphocyte Count
  • Lymphopoiesis / physiology*
  • Mice
  • Mice, Knockout
  • Natural Killer T-Cells / cytology*
  • Natural Killer T-Cells / metabolism
  • Promyelocytic Leukemia Zinc Finger Protein
  • Radiation Chimera
  • T-Box Domain Proteins / biosynthesis
  • T-Box Domain Proteins / deficiency
  • T-Box Domain Proteins / genetics
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / growth & development

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Idb2 protein, mouse
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Kruppel-Like Transcription Factors
  • Promyelocytic Leukemia Zinc Finger Protein
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Zbtb16 protein, mouse
  • Idb3 protein, mouse
  • Interleukin-4
  • Interferon-gamma

Associated data

  • GEO/GSE50933