SIRT1 deficiency in CD4+T cells induces acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
;
(12): 697-703, 2018.
Article
in Chinese
| WPRIM
| ID: wpr-813208
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transplantation, Homologous
/
Histocompatibility Antigens Class I
/
CD4-Positive T-Lymphocytes
/
Down-Regulation
/
Up-Regulation
/
Acute Disease
/
Hematopoietic Stem Cell Transplantation
/
Interleukin-17
/
STAT3 Transcription Factor
/
Sirtuin 1
Limits:
Humans
Language:
Chinese
Journal:
Journal of Central South University(Medical Sciences)
Year:
2018
Type:
Article
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