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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 / 中华儿科杂志
Chinese Journal of Pediatrics ; (12): 181-185, 2011.
Artigo em Chinês | WPRIM | ID: wpr-286134
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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).</p><p><b>CONCLUSION</b>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.</p>
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Timosina / Células da Medula Óssea / Transdução de Sinais / Estudos de Casos e Controles / Terapia de Imunossupressão / Alergia e Imunologia / Indolamina-Pirrol 2,3,-Dioxigenase / Receptor Toll-Like 9 / Células-Tronco Mesenquimais Tipo de estudo: Estudo observacional Limite: Adolescente / Criança / Feminino / Humanos / Masculino Idioma: Chinês Revista: Chinese Journal of Pediatrics Ano de publicação: 2011 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Timosina / Células da Medula Óssea / Transdução de Sinais / Estudos de Casos e Controles / Terapia de Imunossupressão / Alergia e Imunologia / Indolamina-Pirrol 2,3,-Dioxigenase / Receptor Toll-Like 9 / Células-Tronco Mesenquimais Tipo de estudo: Estudo observacional Limite: Adolescente / Criança / Feminino / Humanos / Masculino Idioma: Chinês Revista: Chinese Journal of Pediatrics Ano de publicação: 2011 Tipo de documento: Artigo