Combination Treatment With Metformin and Tacrolimus Improves Systemic Immune Cellular Homeostasis by Modulating Treg and Th17 Imbalance

被引：25

作者：

Lee, Soon Kyu ^{[1
]}

Park, Min-Jung ^{[2
]}

Jhun, Joo Yeon ^{[2
]}

Beak, Jin-Ah ^{[2
]}

Choi, Jeong Won ^{[2
]}

Rye, Jae-Yoon ^{[2
]}

Jang, Jeong Won ^{[1
]}

Bae, Si Hyun ^{[3
]}

Yoon, Seung Kew ^{[1
]}

Choi, Ho Joong ^{[4
]}

You, Young Kyoung ^{[4
]}

Cho, Mi-La ^{[2
]}

Choi, Jong Young ^{[1
]}

机构：

[1] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Div Hepatol,Dept Internal Med, Seoul, South Korea

[2] Catholic Univ Korea, Catholic Res Inst Med Sci, Coll Med, Rheumatism Res Ctr, Seoul, South Korea

[3] Catholic Univ Korea, Eunpyeong St Marys Hosp, Coll Med, Div Hepatol,Dept Internal Med, Seoul, South Korea

[4] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Surg, Seoul, South Korea

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 11卷

基金：

新加坡国家研究基金会;

关键词：

metformin; tacrolimus; regulatory T cell; Th17; cell; allogeneic response; GVHD; liver transplantation; VERSUS-HOST-DISEASE; LIVER; CYCLOSPORINE; THERAPY; DRUG;

D O I：

10.3389/fimmu.2020.581728

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We examined the effect of combination therapy with metformin and tacrolimus on immune parameters including T regulatory (Treg) and type 17 helper T (Th17) cells in vitro and in vivo in mice and in liver transplantation (LT) patients. T cell proliferation and subtypes after in vitro T cell activation or allogeneic stimulation were evaluated. RNA sequencing and microarray analysis were used to evaluate differences in gene expression. Metformin and tacrolimus were administered to mice with graft-versus-host disease (GVHD) and the effects in vivo were assessed. Five LT patients were treated with metformin and the changes in Treg and Th17 cells examined. Combination therapy decreased Type 1 helper T (Th1) and Th17 cells present after in vitro T cell activation, whereas genes associated with Treg were overexpressed. During in vitro allogeneic stimulation, combination therapy increased Treg cells and decreased T cell proliferation and pro-inflammatory markers. In mice with GVHD, combination treatment decreased the clinical and pathological severity of GVHD. In LT patients, addition of metformin increased the peripheral percentage of CD4+Treg and CD8+Treg cells and decreased CD4+Th17. Our study suggests that the addition of metformin to tacrolimus may improve immunological balance by increasing Treg cells and decreasing Th17 cells.

引用

页数：11

共 20 条

[1] Differing Effects of Rapamycin or Calcineurin Inhibitor on T-Regulatory Cells in Pediatric Liver and Kidney Transplant Recipients [J].