Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway

Adipose-derived mesenchymal stem cells (A-MSCs) are promising cellular therapies for the treatment of immune-mediated diseases. Non-gene editing technologies can improve the immune regulatory function of A-MSCs. Our preliminary experiments revealed that an active form of vitamin B6—pyridoxal-5′-phos...

Full description

Saved in:
Bibliographic Details
Main Authors: Cong Li, Jinxian Huang, Huasu Zhu, Qing Shi, Dong Li, Xiuli Ju
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/3121246
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832566809572671488
author Cong Li
Jinxian Huang
Huasu Zhu
Qing Shi
Dong Li
Xiuli Ju
author_facet Cong Li
Jinxian Huang
Huasu Zhu
Qing Shi
Dong Li
Xiuli Ju
author_sort Cong Li
collection DOAJ
description Adipose-derived mesenchymal stem cells (A-MSCs) are promising cellular therapies for the treatment of immune-mediated diseases. Non-gene editing technologies can improve the immune regulatory function of A-MSCs. Our preliminary experiments revealed that an active form of vitamin B6—pyridoxal-5′-phosphate (PLP)—plays an important role in regulating gene expression and cytokine secretion in A-MSCs in vivo. To further clarify the effect of PLP on receptors and cytokines related to the immune regulatory function of A-MSCs, a series of experiments were designed to verify the relationships between PLP and A-MSCs in vitro. Initially, A-MSCs were obtained, and cytokine secretion and the expression of IDO1, NF-κB, and Toll-like receptors in PLP-stimulated A-MSCs were evaluated. In addition, coculture was used to detect A-MSCs-mediated apoptosis of CD3+CD8+ T lymphocytes. These results showed that A-MSCs stimulated with PLP were highly proliferative, consistent with their pluripotent capacity. Further, the surface receptors TLR3, TLR4, IDO1, and NF-κB were upregulated, while TLR6 was downregulated. Concurrently, A-MSCs preconditioned with PLP had the greatest inhibitory effect on CD3+CD8+ T lymphocyte proliferation, indicating that PLP altered the immune regulatory function of A-MSCs through the regulation of TLRs and IDO1 expression.
format Article
id doaj-art-3ab348c5f5164614a91743ec001a7698
institution Kabale University
issn 1687-966X
1687-9678
language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-3ab348c5f5164614a91743ec001a76982025-02-03T01:03:07ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/31212463121246Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB PathwayCong Li0Jinxian Huang1Huasu Zhu2Qing Shi3Dong Li4Xiuli Ju5Department of Pediatrics, Qilu Hospital of Shandong University, Shandong 250012, ChinaDepartment of Pediatrics, Qilu Hospital of Shandong University, Shandong 250012, ChinaDepartment of Pediatrics, Qilu Hospital of Shandong University, Shandong 250012, ChinaStem Cell and Regenerative Medicine Research Center of Shandong University, Jinan, Shandong 250012, ChinaStem Cell and Regenerative Medicine Research Center of Shandong University, Jinan, Shandong 250012, ChinaDepartment of Pediatrics, Qilu Hospital of Shandong University, Shandong 250012, ChinaAdipose-derived mesenchymal stem cells (A-MSCs) are promising cellular therapies for the treatment of immune-mediated diseases. Non-gene editing technologies can improve the immune regulatory function of A-MSCs. Our preliminary experiments revealed that an active form of vitamin B6—pyridoxal-5′-phosphate (PLP)—plays an important role in regulating gene expression and cytokine secretion in A-MSCs in vivo. To further clarify the effect of PLP on receptors and cytokines related to the immune regulatory function of A-MSCs, a series of experiments were designed to verify the relationships between PLP and A-MSCs in vitro. Initially, A-MSCs were obtained, and cytokine secretion and the expression of IDO1, NF-κB, and Toll-like receptors in PLP-stimulated A-MSCs were evaluated. In addition, coculture was used to detect A-MSCs-mediated apoptosis of CD3+CD8+ T lymphocytes. These results showed that A-MSCs stimulated with PLP were highly proliferative, consistent with their pluripotent capacity. Further, the surface receptors TLR3, TLR4, IDO1, and NF-κB were upregulated, while TLR6 was downregulated. Concurrently, A-MSCs preconditioned with PLP had the greatest inhibitory effect on CD3+CD8+ T lymphocyte proliferation, indicating that PLP altered the immune regulatory function of A-MSCs through the regulation of TLRs and IDO1 expression.http://dx.doi.org/10.1155/2019/3121246
spellingShingle Cong Li
Jinxian Huang
Huasu Zhu
Qing Shi
Dong Li
Xiuli Ju
Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway
Stem Cells International
title Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway
title_full Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway
title_fullStr Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway
title_full_unstemmed Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway
title_short Pyridoxal-5′-Phosphate Promotes Immunomodulatory Function of Adipose-Derived Mesenchymal Stem Cells through Indoleamine 2,3-Dioxygenase-1 and TLR4/NF-κB Pathway
title_sort pyridoxal 5 phosphate promotes immunomodulatory function of adipose derived mesenchymal stem cells through indoleamine 2 3 dioxygenase 1 and tlr4 nf κb pathway
url http://dx.doi.org/10.1155/2019/3121246
work_keys_str_mv AT congli pyridoxal5phosphatepromotesimmunomodulatoryfunctionofadiposederivedmesenchymalstemcellsthroughindoleamine23dioxygenase1andtlr4nfkbpathway
AT jinxianhuang pyridoxal5phosphatepromotesimmunomodulatoryfunctionofadiposederivedmesenchymalstemcellsthroughindoleamine23dioxygenase1andtlr4nfkbpathway
AT huasuzhu pyridoxal5phosphatepromotesimmunomodulatoryfunctionofadiposederivedmesenchymalstemcellsthroughindoleamine23dioxygenase1andtlr4nfkbpathway
AT qingshi pyridoxal5phosphatepromotesimmunomodulatoryfunctionofadiposederivedmesenchymalstemcellsthroughindoleamine23dioxygenase1andtlr4nfkbpathway
AT dongli pyridoxal5phosphatepromotesimmunomodulatoryfunctionofadiposederivedmesenchymalstemcellsthroughindoleamine23dioxygenase1andtlr4nfkbpathway
AT xiuliju pyridoxal5phosphatepromotesimmunomodulatoryfunctionofadiposederivedmesenchymalstemcellsthroughindoleamine23dioxygenase1andtlr4nfkbpathway