Notch 1 and Notch 2 synergistically regulate the differentiation and function of invariant NKT cells. Issue 5 (17th July 2015)

• Record Type: Journal Article
• Authors: Oh, Sae Jin; Ahn, Sehee; Jin, Young‐Hee; Ishifune, Chieko; Kim, Ji Hyung; Yasutomo, Koji; Chung, Doo Hyun
• Is Part Of: Journal of leukocyte biology. Volume 98:Issue 5(2015)
• Page Start: 781
• Page End: 789
• Publication Date: 2015-07-17
• Subjects: cytokines -- RBP‐j -- arthritis; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.1A0914-459RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Notch promotes thymic development and cyotokine production of invariant NKT cells in the periphery. 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.