Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity

被引：5

作者：

Larson, Jemma H. ^{[1
]}

Jin, Sujeong ^{[1
]}

Loschi, Michael ^{[1
]}

Wagers, Sara Bolivar ^{[1
]}

Thangavelu, Govindarajan ^{[1
]}

Zaiken, Michael C. ^{[1
]}

McDonald-Hyman, Cameron ^{[2
]}

Saha, Asim ^{[1
]}

Aguilar, Ethan G. ^{[1
]}

Koehn, Brent ^{[1
]}

Osborn, Mark J. ^{[1
]}

Panoskaltsis-Mortari, Angela ^{[1
]}

Macdonald, Kelli P. A. ^{[3
]}

Hill, Geoffrey R. ^{[4
,5
]}

Murphy, William J. ^{[6
,7
]}

Serody, Jonathan S. ^{[8
,9
,10
,11
]}

Maillard, Ivan ^{[12
]}

Kean, Leslie S. ^{[13
,14
,15
]}

Kim, Sangwon, V ^{[16
]}

Littman, Dan R. ^{[17
,18
]}

Blazar, Bruce R. ^{[1
]}

机构：

[1] Univ Minnesota, Masonic Canc Ctr, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55454 USA

[2] Univ Minnesota, Dept Med, Div Hematol Oncol Transplantat, Minneapolis, MN 55454 USA

[3] QIMR Berghofer Med Res Inst, Immunol Dept, Infect & Inflammat Program, Brisbane, Qld, Australia

[4] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA USA

[5] Univ Washington, Div Med Oncol, Seattle, WA USA

[6] Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA USA

[7] Univ Calif Davis, Sch Med, Dept Internal Med, Div Hematol & Oncol, Sacramento, CA USA

[8] Univ North Carolina Chapel Hill, Dept Microbiol & Immunol, Chapel Hill, NC USA

[9] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[10] Univ North Carolina Chapel Hill, Dept Med, Chapel Hill, NC USA

[11] Univ North Carolina Chapel Hill, Computat Med Program, Chapel Hill, NC USA

[12] Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA USA

[13] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA

[14] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA

[15] Harvard Med Sch, Dept Pediat, Boston, MA USA

[16] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Microbiol & Immunol, Philadelphia, PA USA

[17] NYU, Skirball Inst, Kimmel Ctr Biol & Med, Sch Med,Mol Pathogenesis Program, New York, NY USA

[18] NYU, Howard Hughes Med Inst, Sch Med, New York, NY USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2023年 / 23卷 / 08期

基金：

美国国家卫生研究院;

关键词：

regulatory T cell; GPR15; CCR9; GVHD; lymphocyte homing; ALLOGENEIC BONE-MARROW; NECROSIS-FACTOR-ALPHA; CHEMOKINE RECEPTOR 9; RETINOIC ACID; TARGET ORGANS; EXPRESSION; GVHD; TRANSPLANTATION; VEDOLIZUMAB; TOLERANCE;

D O I：

10.1016/j.ajt.2023.01.030

中图分类号：

R61 [外科手术学];

学科分类号：

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.

引用

页码：1102 / 1115

页数：14

共 93 条

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