Notch1 signaling and regulatory T cell function

Naoki Asano, Tomohiro Watanabe, Atsushi Kitani, Ivan J. Fuss, Warren Strober

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

Previous studies have shown that the Notch1 and TGF-β signaling pathways are mutually re-enforcing. Given recent evidence that regulatory T cell (Treg) effector function is mediated by TGF-β signaling, we investigated whether Notch1 signaling also participated in Treg effector function. Initial studies showed that Notch1 ligands, particularly Jagged1, are present on Tregs and that, indeed, blockade of Notch1 signaling with an anti-Jagged1 or a blocking anti-Notch1 Ab inhibits Treg suppressor function in vitro. We then showed that a signaling component generated by Notch1 activation (Notch1 intracellular domain) of dendritic cells physically interacts with a signaling component generated by TGF-β signaling (pSmad3). Furthermore, this interaction has functional downstream effects because over-expression of Notch1 intracellular domain facilitates pSmad3 translocation to the nucleus and enhances pSmad3 transcriptional activity of a Smad-sensitive promoter linked to a luciferase reporter. Finally, we showed that blockade of TGF-β signaling and Notch signaling did not have additive inhibitory effects on Treg suppressor function. These results are consistent with the conclusion that Notch1 signaling facilitates TGF-β-mediated effector function of Tregs.

Original languageEnglish
Pages (from-to)2796-2804
Number of pages9
JournalJournal of Immunology
Volume180
Issue number5
DOIs
Publication statusPublished - 2008 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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