SIRT1 deficiency in CD4+T cells induces acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
10.11817/j.issn.1672-7347.2018.07.001
- Author:
Yuanyuan ZHANG
1
;
Jing YANG
1
;
Guoping ZHANG
1
;
Jie PENG
1
;
Xu CHEN
1
;
Fangping CHEN
1
;
Yajing XU
1
Author Information
1. Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Acute Disease;
CD4-Positive T-Lymphocytes;
metabolism;
Down-Regulation;
Graft vs Host Disease;
etiology;
metabolism;
Hematopoietic Stem Cell Transplantation;
Histocompatibility Antigens Class I;
Humans;
Interleukin-17;
metabolism;
Nuclear Receptor Subfamily 1, Group F, Member 3;
metabolism;
STAT3 Transcription Factor;
metabolism;
Sirtuin 1;
deficiency;
metabolism;
Transplantation, Homologous;
Up-Regulation
- From:
Journal of Central South University(Medical Sciences)
2018;43(7):697-703
- CountryChina
- Language:Chinese
-
Abstract:
To study the relationship between acute graft-versus-host disease (aGVHD) and the SIRT1 expression in peripheral blood CD4+T cells from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods: We collected 40 patients who underwent allo-HSCT from human leukocyte antigen (HLA)-identical sibling donors. SIRT1 expression level in CD4+T cells was measured by real-time PCR and Western blot. Acetylation and phosphorylation of STAT3 in CD4+T cells were detected by Western blot. The binding level between SIRT1 and STAT3 in CD4+T cells was analyzed by co-immunoprecipitation and Western blot. Over-expression of SIRT1 in aGVHD CD4+T cells, as well as STAT3 acetylation and phosphorylation were measured by Western blot. The mRNA levels of RORγt, IL-17A, IL-17F related to Th17 were detected by real-time PCR.
Results: SIRT1 expression was significantly down-regulated, while STAT3 expression, acetylation and phosphorylation levels were significantly up-regulated in patients with aGVHD compared with patients without aGVHD. The STAT3 acetylation was positively correlated with STAT3 phosphorylation (r=0.69, P<0.01). Less SIRT1-STAT3 complexes were found in CD4+T cells from patients with aGVHD compared with patients without aGVHD. After SIRT1 over-expression in aGVHD CD4+T cells, the STAT3 acetylation and phosphorylation, and the expression of RORγt, IL-17A, and IL-17F related to Th17 were significantly down-regulated (P<0.05).
Conclusion: SIRT1 deficiency in CD4+T cells plays a crucial role in up-regulation of STAT3 acetylation and phosphorylation, the increase of Th17 related gene expression, and induction of aGVHD after allogeneic hematopoietic stem cell transplantation.
