Novel therapeutic strategy for Crohn's disease by targeting an NK cell subset

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NAGAHORI Masakazu 東京医科歯科大学, 医学部, 特任准教授 (60420254)
• 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)
• Research Collaborator: YAMAZAKI Motomi ; ONIZAWA Michio ; SUZUKI Masahiro ; WATABE Taro ; HOSOYA Akinori ; JOSE Nisha ; WANG Shuan ; TOKAI Arisa ; TSUGE Naoto ; KAWAI Risa
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 炎症性腸疾患 / クローン病 / 新規治療法 / 粘膜免疫 / NK細胞

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.

Free Research Field

消化器内科学