Development of new treatment with trafficking modulation of colitogenic memory lymphocytes.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460963
• 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: FUJII TOSHIMITSU 東京医科歯科大学, 医学部附属病院, 助教 (30547451)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 下部消化管学 / 炎症性腸疾患 / 新規治療 / 腸管免疫 / リンパ球動態制御

Outline of Final Research Achievements

Fingolimod is a sphingosine-1-phosphate receptor modulator, which inhibits T cell egress from lymph nodes, thereby prevents pathogenic T cells from migrating towards disease sites. In inflammatory bowel diseases (IBD), it is thought that colitogenic memory T cells are reactivated in regional lymphoid organs, and return to inflammatory tissues. We demonstrated that fingolimod prevents the development of colitis induced by the adoptive transfer of naive T cells (naive T colitis) and colitogenic effector-memory T cells (memory T colitis) into SCID mice. Next, we demonstrated that fingolimod decreased T cells in peripheral blood, but conversely increased in bone marrow in the mice lacking lymph nodes and spleen. Notably, fingolimod prevented the development of memory T colitis without lymph nodes and spleen. Collectively, fingolimod may offer an additional role to direct trafficking of T cells in bone marrow, resulting in the prevention of memory T cell-mediated diseases including IBD.

Free Research Field

消化器病学、炎症性腸疾患、腸管免疫