An experimental study on the regulation of bone marrow-derived mesenchymal stem cells through indoleamine 2,3-dioxygenase signaling pathway by thymosin α1 for improving the immunosuppression mediated by T cell.
- Author:
Fang HOU
1
;
Jian-Ming HUANG
;
Rong ZHANG
;
Lan LI
;
Ge LI
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Anemia, Aplastic; metabolism; Bone Marrow Cells; drug effects; metabolism; Case-Control Studies; Child; Female; Humans; Immune Tolerance; Immunosuppression; Indoleamine-Pyrrole 2,3,-Dioxygenase; metabolism; Male; Mesenchymal Stromal Cells; drug effects; metabolism; Signal Transduction; immunology; Thymosin; analogs & derivatives; pharmacology; Toll-Like Receptor 9; metabolism
- From: Chinese Journal of Pediatrics 2011;49(3):181-185
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the regulatory effect of thymosin α1 (Tα1) on immunosuppression of bone marrow mesenchymal stem cells (MSCs) from children with aplastic anemia (AA) through Toll-like receptor 9(TLR9)and indoleamine 2,3-dioxygenase (IDO) signaling pathway.
METHODBone marrow T cell subsets from children with AA and normal individuals were measured by using flow cytometry. Expressions of TLR9/IDO mRNA of MSCs cocultured with Tα1 were determined by reverse-transcription PCR (RT-PCR). Inhibition of PHA-activated T cell proliferation and activation by MSCs cocultured with Tα1 was detected by using MTT assay and flow cytometry.
RESULTCD4(+)/CD8(+) ratio (0.64 ± 0.02) in children with AA was significantly lower than that in normal individuals (1.42 ± 0.05); but CD8(+)/CD38(+) ratio (0.92 ± 0.04) was significantly higher than that in normal individuals (0.65 ± 0.05). AA MSCs obviously expressed TLR9, but not IDO; AA MSCs treated with Tα1 downregulated TLR9 expression but upregulated IDO expression in concentration- and time-dependent manners. The inhibition of AA MSCs on T cell proliferation (21.38% ± 12.34%) was lower than that in normal individuals (62.72% ± 17.79%, P < 0.05), while AA MSCs treated with Tα1 for 18 h exhibited a stronger inhibition (42.83% ± 16.54%, P < 0.05).
CONCLUSIONThe immunosuppression mediated by MSCs could be improved by Tα1 through upregulation of IDO expression via TLR9-dependent signaling pathway. This research provides a new idea for targeted immunomodulatory therapy with bone marrow MSCs from children with AA.
