PMID- 35153255
OWN - NLM
STAT- MEDLINE
DCOM- 20220701
LR  - 20220705
IS  - 1348-4540 (Electronic)
IS  - 0918-8959 (Linking)
VI  - 69
IP  - 6
DP  - 2022 Jun 28
TI  - Human umbilical cord mesenchymal stem cells alleviate the imbalance of CD4(+) T 
      cells via protein tyrosine phosphatase non-receptor type 2/signal transducer and 
      activator of transcription 3 signaling in ameliorating experimental autoimmune 
      thyroiditis in rats.
PG  - 613-625
LID - 10.1507/endocrj.EJ20-0695 [doi]
AB  - This study aimed to investigate the therapeutic effect of human umbilical cord 
      mesenchymal stem cells (hUCMSCs) on experimental autoimmune thyroiditis (EAT) and 
      the underlying mechanisms by utilizing a porcine thyroglobulin-induced EAT rat 
      model. The rats received four tail vein injections of vehicle or hUCMSCs at an 
      interval of 7 days and were sacrificed on day 28 after the first injection. 
      Hematoxylin and eosin staining and enzyme-linked immunosorbent assays (ELISAs) 
      were used to assess the therapeutic effects of hUCMSCs on EAT. Splenic 
      lymphocytes were isolated from rats, and the proportions of CD4(+) T cell subsets 
      were analyzed by flow cytometry. Splenic CD4(+) T cells from EAT rats were 
      cocultured with hUCMSCs. A loss-of-function assay for protein tyrosine 
      phosphatase non-receptor type 2 (PTPN2) was performed to explore the involvement 
      of PTPN2/signal transducer and activator of transcription 3 (STAT3) signaling on 
      the therapeutic benefit of hUCMSCs in EAT. hUCMSC treatment significantly 
      alleviated inflammation, reduced serum thyroid antibody levels, and decreased the 
      ratios of IL-17alpha(+)/CD25(+)FOXP3(+) cells and serum IFN-gamma/IL-4 in EAT rats. 
      Furthermore, hUCMSC treatment upregulated PTPN2 protein expression in splenic 
      lymphocytes of EAT rats as well as enhanced the PTPN2 protein level and 
      attenuated phosphorylation of STAT3 in CD4(+) T cells in vitro. Importantly, 
      knockdown of Ptpn2 significantly reversed hUCMSC-mediated suppression of cell 
      proliferation and hUCMSC-induced alterations in the expression of inflammatory 
      cytokines in CD4(+) T cells. Thus, hUCMSC treatment alleviates thyroid 
      inflammation and the CD4(+) T cell imbalance in EAT via PTPN2/STAT3 signaling, 
      serving as a promising therapeutic approach for autoimmune thyroiditis.
FAU - Gao, Junjie
AU  - Gao J
AD  - Medical College, Qingdao University, Qingdao, China.
FAU - Hu, Jianxia
AU  - Hu J
AD  - The Laboratory of Thyroid Disease, Affiliated Hospital of Qingdao University, 
      Qingdao, China.
FAU - Li, Peng
AU  - Li P
AD  - Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Che, Kui
AU  - Che K
AD  - The Laboratory of Thyroid Disease, Affiliated Hospital of Qingdao University, 
      Qingdao, China.
FAU - Wang, Fei
AU  - Wang F
AD  - Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Yan, Shengli
AU  - Yan S
AD  - Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao 
      University, Qingdao, China.
LA  - eng
PT  - Journal Article
DEP - 20220310
PL  - Japan
TA  - Endocr J
JT  - Endocrine journal
JID - 9313485
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 2)
RN  - EC 3.1.3.48 (Ptpn2 protein, rat)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/metabolism
MH  - *Hashimoto Disease/metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - *Mesenchymal Stem Cells
MH  - *Protein Tyrosine Phosphatase, Non-Receptor Type 2/metabolism
MH  - Rats
MH  - *STAT3 Transcription Factor/metabolism
MH  - Swine
MH  - T-Lymphocytes/metabolism
MH  - *Thyroiditis, Autoimmune/metabolism/therapy
MH  - Umbilical Cord/metabolism
OTO - NOTNLM
OT  - Autoimmune thyroiditis
OT  - CD4-positive lymphocytes
OT  - Human umbilical cord mesenchymal stem cells
OT  - Protein tyrosine phosphatase non-receptor type 2
OT  - Signal transducer and activator of transcription 3
EDAT- 2022/02/15 06:00
MHDA- 2022/07/02 06:00
CRDT- 2022/02/14 05:27
PHST- 2022/02/15 06:00 [pubmed]
PHST- 2022/07/02 06:00 [medline]
PHST- 2022/02/14 05:27 [entrez]
AID - 10.1507/endocrj.EJ20-0695 [doi]
PST - ppublish
SO  - Endocr J. 2022 Jun 28;69(6):613-625. doi: 10.1507/endocrj.EJ20-0695. Epub 2022 
      Mar 10.