PMID- 30393022
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 214
DP  - 2018 Dec 1
TI  - Human placenta-derived mesenchymal stem cells ameliorate GVHD by modulating 
      Th17/Tr1 balance via expression of PD-L2.
PG  - 98-105
LID - S0024-3205(18)30692-1 [pii]
LID - 10.1016/j.lfs.2018.10.061 [doi]
AB  - AIMS: To examine whether human placenta mesenchymal stem/stromal cells (hpMSCs) 
      mitigate graft-versus-host-disease (GVHD) via regulation of Th17 and Tr1. 
      MATERIALS AND METHODS: hpMSCs or phosphate buffered saline (PBS, as a control) 
      were injected into humanized xeno-GVHD NOD/SCID mouse model. Effects on body 
      weights and survival times were determined. In addition, various assays, 
      including flow cytometry (FCM) and HE stain, were performed on tissues (liver, 
      spleen, lung and intestine) from these hpMSCs versus PBS treated GVHD mice. Th17 
      cell number in vitro was analyzed by FCM. KEY FINDINGS: hpMSCs reduced weight 
      loss, along with IL-6 and IL-17 production to prolong the survival of GVHD mice. 
      Th17 cell number was down-regulated obviously in hpMSCs treated GVHD mice. 
      Conversely, Tr1 cell number and TGF-beta production were enhanced by hpMSCs. 
      Moreover, knockdown of programmed death ligand 2 (PD-L2) increased Th17 cell 
      number from PMA activated T cells co-cultured with hpMSCs. SIGNIFICANCE: hpMSCs 
      can modulate the balance between Th17 and Tr1 cells to alleviate GVHD. In 
      addition, PD-L2 as expressed on hpMSCs inhibits the generation of Th17 subset 
      from activated T cells. These data suggest that hpMSCs attenuate GVHD through 
      inhibition of severe inflammatory responses resulting from T cell 
      differentiation.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Ma, Yanchao
AU  - Ma Y
AD  - Department of Immunology, Binzhou Medical University, Yantai, Shandong, Province, 
      264003, People's Republic of China.
FAU - Wang, Zhuoya
AU  - Wang Z
AD  - Department of Immunology, Binzhou Medical University, Yantai, Shandong, Province, 
      264003, People's Republic of China.
FAU - Zhang, Aiping
AU  - Zhang A
AD  - Department of Immunology, Binzhou Medical University, Yantai, Shandong, Province, 
      264003, People's Republic of China.
FAU - Xu, Fenghuang
AU  - Xu F
AD  - Urology Department, The first affiliated hospital of Hainan Medical University, 
      Haikou, Hainan Province 570102, People's Republic of China.
FAU - Zhao, Nannan
AU  - Zhao N
AD  - Department of Immunology, Binzhou Medical University, Yantai, Shandong, Province, 
      264003, People's Republic of China.
FAU - Xue, Jiangnan
AU  - Xue J
AD  - Department of Immunology, Binzhou Medical University, Yantai, Shandong, Province, 
      264003, People's Republic of China.
FAU - Zhang, Hongqin
AU  - Zhang H
AD  - Department of Histology and Embryology, Binzhou Medical University, Yantai, 
      Shandong Province 264003, People's Republic of China. Electronic address: 
      byzhhq@163.com.
FAU - Luan, Xiying
AU  - Luan X
AD  - Department of Immunology, Binzhou Medical University, Yantai, Shandong, Province, 
      264003, People's Republic of China. Electronic address: xyluan@sohu.com.
LA  - eng
PT  - Journal Article
DEP - 20181027
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Cytokines)
RN  - 0 (PDCD1LG2 protein, human)
RN  - 0 (Programmed Cell Death 1 Ligand 2 Protein)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Graft vs Host Disease/metabolism/mortality/*therapy
MH  - Humans
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/cytology/physiology
MH  - Mice, SCID
MH  - Placenta/cytology
MH  - Pregnancy
MH  - Programmed Cell Death 1 Ligand 2 Protein/*metabolism
MH  - T-Lymphocytes, Regulatory/*physiology
MH  - Th17 Cells/*physiology
MH  - Weight Loss
OTO - NOTNLM
OT  - Graft-versus-host-disease (GVHD)
OT  - Mesenchymal stem cells (MSCs)
OT  - Placenta
OT  - Programmed death ligand 2 (PD-L2)
OT  - Th17
OT  - Tr1
EDAT- 2018/11/06 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/11/06 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2018/10/19 00:00 [revised]
PHST- 2018/10/26 00:00 [accepted]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/11/06 06:00 [entrez]
AID - S0024-3205(18)30692-1 [pii]
AID - 10.1016/j.lfs.2018.10.061 [doi]
PST - ppublish
SO  - Life Sci. 2018 Dec 1;214:98-105. doi: 10.1016/j.lfs.2018.10.061. Epub 2018 Oct 
      27.