| Project/Area Number |
24590937
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAGAISHI Takashi 東京医科歯科大学, 医学部附属病院, 助教 (60447464)
WATANABE Mamoru 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
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| Research Collaborator |
YAMAZAKI Motomi
ONIZAWA Michio
SUZUKI Masahiro
WATABE Taro
HOSOYA Akinori
JOSE Nisha
WANG Shuan
TOKAI Arisa
TSUGE Naoto
KAWAI Risa
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 炎症性腸疾患 / クローン病 / 新規治療法 / 粘膜免疫 / NK細胞 |
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| Outline of Final Research Achievements |
We previously reported that IL-7-/-RAG-/- mice receiving naive T cells failed to induce colitis. Such abrogation of colitis may be associated not only with the lack of IL-7, but also with the induction of T cell apoptosis at an early stage of colitis development. Natural killer (NK) cells may be associated with the suppression of pathogenic T cells, and may induce apoptosis of CD4+ T cells. To further investigate these roles of NK cells, RAG-/- and IL-7-/-RAG-/- mice that had received naive T cells were depleted of NK cells. NK cell depletion at an early stage during effecter/memory T cell (TEM) development resulted in exacerbated colitis in recipient mice even in the absence of IL-7. Increased TEM were observed in the T cell-reconstituted RAG-/- recipients when NK cells were depleted. These results suggest that NK cells suppress colitis severity in the T cell-reconstituted recipient mice through targeting of colitogenic TEM present at the early stage of T cell development.
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