2011 Fiscal Year Final Research Report
Generation and application of artificial lymphoid tissues
| Project Area | Immunological Self Recognition and its Disorders |
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| Project/Area Number |
19059015
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University (2008-2011)
The Institute of Physical and Chemical Research (2007) |
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Principal Investigator |
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| Project Period (FY) |
2007 – 2011
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| Keywords | 人工免疫組織 / 人工リンパ節 / ストローマ細胞 / インデューサー細胞 / 抗原特異的二次免疫反応 / 感染防御 / 腫瘍免疫 / 人工脾臓 |
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| Research Abstract |
The generation of functional artificial lymphoid tissue will be a major focus of future research in Immunology. In human, this will be an alternative tool which induces specific immune responses at ectopic sites and offers a novel way to restore the immune status and to treat uncontrollable obstinate diseases such as cancer, autoimmune diseases, severe infection and immunodeficiency caused by primary defect or aging. Artificially synthesized lymphoid tissue may also provide us with a highly informative method to further study development and physiological functions of lymphoid tissues and organs. We recently reported successful generation of artificial lymph node-like tissues at ectopic sites in mouse. They showed a remarkable ability to induce secondary immune responses upon antigen stimulation, especially when transplanted into naive or immuno-deficient hosts. It was found that a large numbers of memory T cells and follicular helper T cells besides of memory B cells are highly enrich
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ed in our artificial lymph nodes, supporting their ability to induce a strong antigen-specific immune response. In our previous trial, we have utilized a mouse lymphoid stromal cell line and dendritic cells as an organizer for formation of lymphoid tissues and collagen sponge as a scaffold. Recently, we have also succeeded to synthesize artificial lymph nodes, instead of using stromal cells, by using a combination of various kinds of soluble chemokines and cytokines, which are attached to slow-releasing biomaterial (soft gel). The structure of newly synthesized artificial lymphoid tissues is stable in vivo more than one month. Antigen specific immune response could be induced in the tissues. Thus, we have successfully generated a complete structure of lymph node-like tissues without using any stromal cell component. We plan to apply this new method to generate human type secondary lymphoid tissues, which display immunological function, in humanized mice. We have also established the novel method to generate a complete structure of mouse spleen by using “single stromal cell-aggregates” derived from spleen capsules of newborn mice (3-6days after birth). We are now trying to identify and analyze the cells responsible for generation of adult type spleen from newborn mouse spleen capsules. Less
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[Journal Article] Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity2011
Author(s)
A. Otsuka, M. Kubo, T. Honda, G. Egawa, S. Nakajima, H. Tanizaki, B. Kim, S. Matsuoka, T. Watanabe, S. Nakae, Y. Miyachi and K. Kabashima
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Journal Title
PLoS ONE
Volume: vol.6, No.9
Pages: e25538
DOI
Peer Reviewed
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[Journal Article] Dys-regulated generation of follicular helper T cells in the spleen triggers fatal autoimmune hepatitis in mice2011
Author(s)
N. Aoki, M. Kido, S. Iwamoto, H. Nishiura, R. Maruoka, J. Tanaka, T. Watanabe, Y. Tanaka, T. Okazaki, T. Chiba, N. Watanabe
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Journal Title
Gastroenterology
Volume: vol.140, No.4
Pages: 1322-1333
DOI
Peer Reviewed
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[Journal Article] Prostaglandin I receptor IP promoted Th1- differentiation through camp2010
Author(s)
S. Nakajima, T. Honda, D. Sakata, G. Egawa, H. Tanizaki, A. Otsuka, C.S. Morinaga, T. Watanabe, Y. Miyachi, S. Narumiya, K. Kabashima
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Journal Title
J. Immunol.
Volume: vol.184
Pages: 5595-5603
DOI
Peer Reviewed
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[Journal Article] Activated Regulatory T cells are the major T cell type emigrating from sensitized skin.2010
Author(s)
M. Tomura, T. Honda, H. Tanizaki, A. Otsuka, G. Egawa, Y. Tokura, S. hori, J. G. Cyster, T. Watanabe, Y. Miyachi, O. Kanagawa, K. Kabashima
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Journal Title
J. Clin. Invest.
Volume: vol.120
Pages: 883-893
DOI
Peer Reviewed
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