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Reseach Projects: Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. A significant decrease of number in CD3+, CD4+, CD8+ cells and naïve T lymphocytes occurs with increase in age. It also is recognized that CD4+ T cells in the elderly are qualitatively altered, including a defects in the TCR signaling intensity, reduced immunologic synapse formation with antigen-presenting cells, diminished cognate helper function, and altered reduction of Th1 and Th2 effector differentiation. Although there are many report for age-related changes in T cells, the mechanisms remain uncertain. In my research group, we are trying to address these questions by studying regulation of gene expression and alternative splicing that control T lymphocyte development. We are focusing on how ThPOK, master regulator for helper T cell development, regulate transcriptional network involved in lineage choice of CD4+CD8+DP thymocytes and how alternative splicing variant affect diversity of T cell differentiation and function. We use not only molecular biological and genetic approach but also microarray, next generation sequencer and bioinformatics tool to clear the questions. | ||
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Contact Address： Yoshinori Naoe, Ph.D. Department of Mechanism of Aging Research Institute National Center for Geriatrics and Gerontology
35 Gengo, Morioka-machi Obu, Aichi, 474-8511, JAPAN Tel: +81-562-46-3211 ext. 5056(Office), 5114(Lab) Fax: +81-562-46-8461 E-mail: ynaoe@ncgg.go.jp | ||
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Publications (Selected) Sakaguchi S, Hombauer M, Bilic I, Naoe Y, Schebesta S, Taniuchi I and Ellmeier W. The zinc finger protein MAZR is part of the transcription factor network controlling CD4/CD8 cell fate decision of DP thymocytes. Nat. Immunol. 2010, 11: 442-448.
Kitoh A, Ono M, Naoe Y, Ohkura N, Yamaguchi T, Yaguchi H, Kitabayashi I, Tsukada T, Nomura T, Miyamachi Y, Taniuchi I and Sakaguchi S. Indispensable role of Runx1/Cbfβ complex for in vivo suppressive function for FoxP3+ regulatory T cells. Immunity. 2009, 31: 609-620.
Bruno L, Mazzarella L, Hoogenkamp M, Hertweck A, Cobb BS, Sauer S, Hadjur S, Leleu M, Naoe Y,, Telfer J, Bonifer C, Taniuchi I, Fisher AG and Merkenschlager M. Runx proteins regulate FoxP3 expression. J Exp Med. 2009, 206: 2329-2337.
Loomis RJ*,Naoe Y,*, Parker JB, Savic V, Bozovsky MR, Macfarlan T, Manley JL, Chakravarti D. Chromatin binding of SRp20 and ASF/SF2 and dissociation from mitotic chromosomes is modulated by histone H3 serine 10 phosphorylation. Mol Cell. 2009, 33: 450-461. (* Equally contributed).
Muroi S, Naoe Y, Miyamoto C, Akiyama K, Ikawa T, Masuda K, Kawamoto H, Taniuchi I. Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate. Nat Immunol. 2008, 9:1113-1121.
Setoguchi R*, Tachibana M*, Naoe Y,*, Muroi S, Akiyama K, Tezuka C, Okuda T, Taniuchi I. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science. 2008, 319: 822-825. (* Equally contributed).
Egawa T, Tilman RE, Naoe Y,, Taniuchi I and Littman DR The role of the Runx transcriptional factors in thymocytes differentiation and in homeostasis of naïve T cells. J Exp Med. 2007, 204: 1945-1957.
Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, Littman DL and Taniuchi I. Repression of interleukin-4 in T helper type I cells by Runx/Cbfb complex to the IL-4 silencer. J Exp Med. 2007, 204: 1749-1755.
Fukushima-Nakase Y, Naoe Y, Taniuchi I, Hosoi H, Sugimoto T, Okuda T. Shared and distinct roles mediated through C-terminal subdomains of acute myeloid leukemia/Runt-related transcription factor molecules in murine development. Blood. 2005, 105: 4298-4307. | ||
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