归巢(生物学)
离体
医学
移植物抗宿主病
造血干细胞移植
免疫学
胃肠道
免疫系统
移植
干细胞
调节性T细胞
疾病
受体
炎症
趋化因子
趋化因子受体
T细胞
体内
内科学
生物
白细胞介素2受体
细胞生物学
生物技术
生态学
作者
Jemma H. Larson,Sujeong Jin,Michaël Loschi,Sara Bolivar-Wagers,Govindarajan Thangavelu,Michael Zaiken,Cameron McDonald-Hyman,Asim Saha,Ethan G. Aguilar,Brent H. Koehn,Mark J. Osborn,Angela Panoskaltsis‐Mortari,Kelli P. A. MacDonald,Geoffrey R. Hill,William J. Murphy,Jonathan S. Serody,Ivan Maillard,Leslie S. Kean,Sangwon V. Kim,Dan R. Littman,Bruce R. Blazar
标识
DOI:10.1016/j.ajt.2023.01.030
摘要
Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T cells reduces graft-versus-host disease incidence. Despite no change in in vitro suppressive function, transfer of ex vivo expanded regulatory T cells transduced to overexpress G protein-coupled receptor 15 or C-C motif chemokine receptor 9, specific homing receptors for colon or small intestine, respectively, lessened graft-versus-host disease severity in mice. Increased regulatory T cell frequency and retention within the gastrointestinal tissues of mice that received gut homing T cells correlated with lower inflammation and gut damage early post-transplant, decreased graft-versus-host disease severity, and prolonged survival compared with those receiving control transduced regulatory T cells. These data provide evidence that enforced targeting of ex vivo expanded regulatory T cells to the gastrointestinal tract diminishes gut injury and is associated with decreased graft-versus-host disease severity.
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