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

Mucosal Immunology
Mark Dell'Aringa, R Lee Reinhardt

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.

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Citations

Jul 6, 2019·European Journal of Immunology·Julia Matthias, Christina E Zielinski
Feb 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric PerkeyIvan Maillard
May 21, 2020·Cellular & Molecular Immunology·Kerry L Hilligan, Franca Ronchese
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Sep 4, 2021·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yvanna Louise Di Christine OliveiraSilvio Santana Dolabella

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Methods Mentioned

BETA
flow cytometry
PCR
mechanical dissociation
FCS

Software Mentioned

FIJI ImageJ
FlowJo
TreeStar

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