Notch signaling represents an important checkpoint between follicular T-helper and canonical T-helper 2 cell fate

Mucosal Immunol. 2018 Jul;11(4):1079-1091. doi: 10.1038/s41385-018-0012-9. Epub 2018 Feb 21.

Abstract

Type-2 immunity is regulated by two distinct CD4+ T-cell subsets. T follicular helper (Tfh) cells are required for humoral hallmarks of type-2 inflammation. T-helper type-2 (Th2) cells orchestrate type-2 inflammation in peripheral tissues, such as the lung and intestine. Given the importance of Notch signaling in the establishment of other CD4+ T-helper cell subsets, we investigated whether canonical Notch activation could differentially impact Tfh and Th2 cell fate during the induction of type-2 immunity. These studies show that Tfh cell, but not Th2 cell, generation and function is reliant on Notch signaling. While early Tfh cell specification is influenced by functional Notch ligands on classical dendritic cells, functional Notch ligands on cells other than dendritic cells, T cells, B cells, and follicular dendritic cells are sufficient to achieve full Tfh cell commitment. These findings identify Notch signaling as an early lineage-determining factor between Tfh and Th2 cell fate.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Dendritic Cells / physiology*
  • Germinal Center / immunology*
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism*
  • Signal Transduction
  • Strongylida Infections / immunology*
  • T-Lymphocyte Subsets / physiology*
  • Th2 Cells / physiology*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Receptor, Notch2
  • Interleukin-4
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases