title: [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].
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Bone 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.
  
  
  RESULTS
  CD4(+)/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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pediatrics, People's Hospital of Sichuan Province, Chengdu 610072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hou
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Huang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Ge
authors.initials: G
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D013947:Thymosin; D000077596:Thymalfasin