Article abstract
Nature Immunology 9, 1140 - 1147 (2008)
Published online: 24 August 2008 | doi:10.1038/ni.1649
Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity
Yoichi Maekawa1,8, Yoshiaki Minato1,2,8, Chieko Ishifune1, Takeshi Kurihara1, Akiko Kitamura1, Hidefumi Kojima3, Hideo Yagita4, Mamiko Sakata-Yanagimoto5,6, Toshiki Saito5, Ichiro Taniuchi7, Shigeru Chiba5,6, Saburo Sone2 & Koji Yasutomo1
Abstract
The acquisition of cytotoxic effector function by CD8+ T cells is crucial for the control of intracellular infection and tumor invasion. However, it remains unclear which signaling pathways are required for the differentiation of CD8+ cytotoxic T lymphocytes. We show here that Notch2-deficient T cells had impaired differentiation into cytotoxic T lymphocytes. In addition, dendritic cells with lower expression of the Notch ligand Delta-like 1 induced the differentiation of cytotoxic T lymphocytes less efficiently. We found that the intracellular domain of Notch2 interacted with a phosphorylated form of the transcription factor CREB1, and together these proteins bound the transcriptional coactivator p300 to form a complex on the promoter of the gene encoding granzyme B. Our results suggest that the highly regulated, dynamic control of T cell cytotoxicity depends on the integration of Notch2 and CREB1 signals.
- Department of Immunology & Parasitology, Tokushima 770-8503, Japan.
- Department of Respiratory Medicine & Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
- Department of Immunology, Dokkyo Medical University, Tochigi 321-0293, Japan.
- Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
- Department of Cell Therapy and Transplantation Medicine, University of Tokyo, Tokyo 113-8655, Japan.
- Department of Clinical and Experimental Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
- Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
- These authors contributed equally to this work.
Correspondence to: Koji Yasutomo1 e-mail: yasutomo@basic.med.tokushima-u.ac.jp
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Can we apply the T H 1-T H 2 paradigm to all lymphocytes?Nature Immunology News and Views (01 Oct 2001)
Can we apply the T H 1-T H 2 paradigm to all lymphocytes?Nature Immunology News and Views (01 Oct 2001)
See all 3 matches for News And ViewsRESEARCH
Effector and memory CD8 + T cell fate coupled by T-bet and eomesoderminNature Immunology Article (01 Dec 2005)
Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitisNature Letters to Editor (08 Jan 2009)
See all 35 matches for Research
