PMID- 36277038
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221025
IS  - 1687-966X (Print)
IS  - 1687-9678 (Electronic)
VI  - 2022
DP  - 2022
TI  - hUC-MSCs Attenuate Acute Graft-Versus-Host Disease through Chi3l1 Repression of 
      Th17 Differentiation.
PG  - 1052166
LID - 10.1155/2022/1052166 [doi]
LID - 1052166
AB  - Mesenchymal stem cells (MSCs) have already demonstrated definitive evidence of 
      their clinical benefits in acute graft-versus-host disease (aGvHD) and other 
      inflammatory diseases. However, the comprehensive mechanism of MSCs' 
      immunomodulation properties has not been elucidated. To reveal their potential 
      immunosuppressive molecules, we used RNA sequencing to analyze gene expression in 
      different tissue-derived MSCs, including human bone marrow, umbilical cord, 
      amniotic membrane, and placenta, and found that chitinase-3-like protein 1 
      (Chi3l1) was highly expressed in human umbilical cord mesenchymal stem cells 
      (hUC-MSCs). We found that hUC-MSCs treated with interferon-gamma (IFN-gamma) and 
      tumor necrosis factor-alpha (TNF-alpha) exhibited increased expression of Chi3l1 and 
      concurrently repressed T-helper 17 cell (Th17) differentiation through inhibition 
      of signal transducer and activator of transcription 3 (STAT3) activation. 
      Furthermore, Chi3l1 knockdown hUC-MSCs exhibited impaired therapeutic efficacy in 
      aGvHD mice with an increased inflammatory response by promoting Th17 cell 
      differentiation, including an increase in IL-17A in the spleen, intestine, and 
      serum. Collectively, these results reveal a new immunosuppressive molecule, 
      Chi3l1, in hUC-MSCs in the treatment of aGvHD that regulates Th17 differentiation 
      and inhibits STAT3 activation. These novel insights into the mechanisms of 
      hUC-MSC immunoregulation may lead to the consistent production of hUC-MSCs with 
      strong immunosuppressive functions and thus improved clinical utility.
CI  - Copyright (c) 2022 Weijiang Liu et al.
FAU - Liu, Weijiang
AU  - Liu W
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
FAU - Yuan, Fulin
AU  - Yuan F
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
FAU - Bai, Haitao
AU  - Bai H
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
AD  - Institute of Life Science, Hebei University, Baoding 071002, China.
FAU - Liu, Yuanlin
AU  - Liu Y
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
FAU - Li, Xue
AU  - Li X
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
FAU - Wang, Yang
AU  - Wang Y
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
FAU - Zhang, Yi
AU  - Zhang Y
AUID- ORCID: 0000-0003-2498-3948
AD  - Department of Experimental Hematology and Biochemistry, Beijing Institute of 
      Radiation Medicine, Beijing 100850, China.
LA  - eng
PT  - Journal Article
DEP - 20221012
PL  - United States
TA  - Stem Cells Int
JT  - Stem cells international
JID - 101535822
PMC - PMC9582900
COIS- The authors declare that they have no competing interests.
EDAT- 2022/10/25 06:00
MHDA- 2022/10/25 06:01
PMCR- 2022/10/12
CRDT- 2022/10/24 04:25
PHST- 2022/03/18 00:00 [received]
PHST- 2022/06/04 00:00 [accepted]
PHST- 2022/10/24 04:25 [entrez]
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2022/10/25 06:01 [medline]
PHST- 2022/10/12 00:00 [pmc-release]
AID - 10.1155/2022/1052166 [doi]
PST - epublish
SO  - Stem Cells Int. 2022 Oct 12;2022:1052166. doi: 10.1155/2022/1052166. eCollection 
      2022.