PMID- 29088831
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 43
DP  - 2017 Sep 26
TI  - Obese donor mice splenocytes aggravated the pathogenesis of acute 
      graft-versus-host disease via regulating differentiation of Tregs and CD4(+) T 
      cell induced-type I inflammation.
PG  - 74880-74896
LID - 10.18632/oncotarget.20425 [doi]
AB  - Acute graft-versus-host disease (aGVHD) remains one of the most severe 
      complications in organ and bone marrow transplantation, leading to much morbidity 
      and mortality. Obesity has been associated with increased risk of development of 
      various inflammatory diseases. Here, we investigated the in vitro and in vivo 
      effects of obese donor splenocytes on the development of acute graft-versus-host 
      disease (aGVHD). In this study, mixed lymphocyte reactions (MLR) in vitro showed 
      that obese donor mouse CD4(+) T cell promoted the production of interleukin-2 
      (IL-2), interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Meanwhile, the 
      inducible Tregs population decreased greatly in obese donor mouse CD4(+) T cells' 
      induction group, compared with normal group. Then in the murine aGVHD model, we 
      found that obese donor splenocytes dramatically increased the severity of aGVHD 
      through down-regulating immune tolerance while enhancing systemic and local 
      immunity. Moreover, we showed that aGVHD induced by obese donors resulted in 
      massive expansion of donor CD3(+) T cells, release of Th1-related cytokines, 
      interleukin-17 (IL-17) and chemokines, significant increase of Th17 cells and 
      inhibition of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) and impaired 
      suppressive ability of donor Tregs. Expression of sphingosine-1-phosphate 
      receptor 1 (S1PR1), phosphorylated Akt, mammalian target of rapamycin (mTOR) and 
      Raptor increased, while the phosphorylation level of SMAD3 was decreased in the 
      skin, intestine, lung and liver from obese donor splenocytes-treated aGVHD mice. 
      Furthermore, at mRNA and protein levels, we defined several molecules that may 
      account for the enhanced ability of obese donor splenocytes to migrate into 
      target organs, such as IL-2, IL-17, IFN-gamma, TNF-alpha, CXCR3, CXCL9, CXCL10, CXCL11 
      and CCL3. Therefore, these results imply that obese donor cells may be related to 
      the risk of aGVHD and helping obese donor individuals lose weight represent a 
      compulsory clinical strategy before implementing transplantation to control aGVHD 
      of recipients.
FAU - Li, Zengyao
AU  - Li Z
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Gu, Jian
AU  - Gu J
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Zhu, Qin
AU  - Zhu Q
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Radiotherapy, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Lu, Hao
AU  - Lu H
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Lu, Yunjie
AU  - Lu Y
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Wang, Xuehao
AU  - Wang X
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing 210029, China.
LA  - eng
PT  - Journal Article
DEP - 20170824
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5650386
OTO - NOTNLM
OT  - aGVHD
OT  - obesity
OT  - transplantation
COIS- CONFLICTS OF INTEREST None declared.
EDAT- 2017/11/02 06:00
MHDA- 2017/11/02 06:01
PMCR- 2017/09/26
CRDT- 2017/11/02 06:00
PHST- 2017/04/21 00:00 [received]
PHST- 2017/06/04 00:00 [accepted]
PHST- 2017/11/02 06:00 [entrez]
PHST- 2017/11/02 06:00 [pubmed]
PHST- 2017/11/02 06:01 [medline]
PHST- 2017/09/26 00:00 [pmc-release]
AID - 20425 [pii]
AID - 10.18632/oncotarget.20425 [doi]
PST - epublish
SO  - Oncotarget. 2017 Aug 24;8(43):74880-74896. doi: 10.18632/oncotarget.20425. 
      eCollection 2017 Sep 26.