Therapeutic potential of transferring of Tregs to SAMP1 mice

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860562
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: Ishikawa Dai 順天堂大学, 医学部, 准教授 (30622675)
• Research Collaborator: OSADA Taro 順天堂大学, 医学部, 先任准教授 (00338336) ; SASAKI Takashi 順天堂大学, 医学部, 助教 (50723897)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 潰瘍性大腸炎 / 制御性リンパ球 / 腸内細菌叢 / 糞便移植療法 / SAMP1マウス / 無菌マウス / クローン病モデルマウス / 細胞移入療法

Outline of Final Research Achievements

The commensal flora plays an important role in the intestinal inflammation. However, we have recently shown that commensal bacteria are not essential for the development of SAMP1 ileitis. In this study, we demonstrate that cotransfer of SPF CD4+ cells prevent the colitis induced by GF SAMP CD4+ cells. GF nTreg cells indicate lower production of immunoregulatory cytokines in culture stimulation assay and significantly impaired suppressive capacities both in the proliferative responses and in inducing the colitis. GF SAMP mice orally receiving enteric flora from SPF mice develop significant colitis in acute phase due to a defect in nTreg cells, but rapidly expanded Treg cells suppressed later colitis. Furthermore, they prevented developing DSS-induced colitis. Our results provide evidence that the absence of commensal flora lead to impaired functions of nTreg cells, which contributes to the development of colitis but not ileitis in SAMP mice.

Free Research Field

消化器内科