PMID- 30124203 OWN - NLM STAT- MEDLINE DCOM- 20181114 LR - 20181114 IS - 1672-7347 (Print) IS - 1672-7347 (Linking) VI - 43 IP - 7 DP - 2018 Jul 28 TI - [SIRT1 deficiency in CD4+T cells induces acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation]. PG - 697-703 LID - 10.11817/j.issn.1672-7347.2018.07.001 [doi] AB - 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 RORgammat, 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 RORgammat, 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. FAU - Zhang, Yuanyuan AU - Zhang Y AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Yang, Jing AU - Yang J AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Zhang, Guoping AU - Zhang G AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Peng, Jie AU - Peng J AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Chen, Xu AU - Chen X AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Chen, Fangping AU - Chen F AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Xu, Yajing AU - Xu Y AD - Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China. LA - chi PT - Journal Article PL - China TA - Zhong Nan Da Xue Xue Bao Yi Xue Ban JT - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JID - 101230586 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (IL17A protein, human) RN - 0 (Interleukin-17) RN - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3) RN - 0 (RORC protein, human) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (histocompatibility antigen DLA) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Acute Disease MH - CD4-Positive T-Lymphocytes/*metabolism MH - Down-Regulation MH - Graft vs Host Disease/*etiology/metabolism MH - *Hematopoietic Stem Cell Transplantation MH - Histocompatibility Antigens Class I MH - Humans MH - Interleukin-17/metabolism MH - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism MH - STAT3 Transcription Factor/*metabolism MH - Sirtuin 1/*deficiency/metabolism MH - Transplantation, Homologous MH - Up-Regulation EDAT- 2018/08/21 06:00 MHDA- 2018/11/15 06:00 CRDT- 2018/08/21 06:00 PHST- 2018/08/21 06:00 [entrez] PHST- 2018/08/21 06:00 [pubmed] PHST- 2018/11/15 06:00 [medline] AID - 10.11817/j.issn.1672-7347.2018.07.001 [doi] PST - ppublish SO - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Jul 28;43(7):697-703. doi: 10.11817/j.issn.1672-7347.2018.07.001.