Notch 1 and Notch 2 synergistically regulate the differentiation and function of invariant NKT cells

Sae Jin Oh, Sehee Ahn, Young Hee Jin, Chieko Ishifune, Ji Hyung Kim, Koji Yasutomo, Doo Hyun Chung

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Invariant natural killer T cells are a distinct subset of T cells that exert Janus-like functions. Moreover, Notch signaling is known to have critical roles in the development and functions of T cells. However, it is not known whether Notch signaling contributes to the development or functions of invariant natural killer T cells. Here, we found that CD4-specific gene ablation of Notch 1 and Notch 2 (N1N2 −/− ) increased the number of invariant natural killer T cells in the thymus but decreased them in the liver. N1N2 −/− mice showed impaired thymic maturation of invariant natural killer T cells from the NK1.1 CD44 + to the NK1.1 + CD44 + stage, resulting in accumulation of NK1.1 CD44 + invariant natural killer T cells in the thymus. Upon activation, hepatic invariant natural killer T cells from N1N2 −/− mice produced lower cytokine levels and increased apoptosis versus wild-type invariant natural killer T cells. Furthermore, Notch 1/Notch 2-deficient, but not wild type, invariant natural killer T cells failed to promote antibody-induced arthritis in CD1d −/− mice. Unlike N1N2 −/− mice, RBP-j lox/lox CD4-Cre mice showed similar percentages and numbers of thymic invariant natural killer T cells to wild-type mice but had defects in their homeostasis, maturation, and cytokine production in the liver. Taken together, our data indicate distinct effects of Notch signaling on invariant natural killer T cells in the thymus and liver, which are at least partly independent of RBP-j in the thymus.

Original languageEnglish
Pages (from-to)781-789
Number of pages9
JournalJournal of Leukocyte Biology
Volume98
Issue number5
DOIs
Publication statusPublished - 2015 Nov 1
Externally publishedYes

Keywords

  • Arthritis
  • Cytokines
  • RBP-j

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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