Mesenchymal Stromal Cells Mitigate Experimental Colitis via Insulin-like Growth Factor Binding Protein 7-mediated Immunosuppression
| Autor: | Weijun Huang, Mei Hua Jiang, Huimin Xia, Andy Peng Xiang, Ying Tuo, Muyun Liu, Maosheng Wang, Wanwen Lin, Yan Liao, Junxia Lei, Dongxi Hong |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
IGFBP7 medicine.medical_treatment Inflammation Mesenchymal Stem Cell Transplantation Insulin-like growth factor-binding protein Proinflammatory cytokine Mice 03 medical and health sciences Paracrine signalling Drug Discovery Genetics medicine Animals Immunologic Factors Molecular Biology Cells Cultured Cell Proliferation Pharmacology biology Growth factor Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Colitis Up-Regulation Insulin-Like Growth Factor Binding Proteins Disease Models Animal 030104 developmental biology Cytokine Immunology biology.protein Cancer research Molecular Medicine Original Article medicine.symptom |
| Zdroj: | Molecular Therapy. 24:1860-1872 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2016.140 |
| Popis: | Mesenchymal stromal cells (MSCs) have shown great potential for treating inflammatory bowel disease, which is ameliorated through paracrine cross talk between MSCs and T-cells. Members of the insulin-like growth factor binding protein (IGFBP) family have important immunomodulatory functions in MSCs, but the underlying mechanisms behind these functions have not yet been clearly elucidated. In this study, we investigate whether MSC-produced IGFBP7 is involved in immune modulation using a mouse experimental colitis model. Gene expression profiling revealed that IGFBP7 was highly expressed in MSCs. Consistent with this findings, IGFBP7 knockdown in MSCs significantly decreased their immunomodulatory properties, decreasing the antiproliferative functions of MSCs against T-cells, while also having an effect on the proinflammatory cytokine production of the T-cells. Furthermore, in the mouse experimental colitis model, MSC-derived IGFBP7 ameliorated the clinical and histopathological severity of induced colonic inflammation and also restored the injured gastrointestinal mucosal tissues. In conclusion, IGFBP7 contributes significantly to MSC-mediated immune modulation, as is shown by the ability of IGFBP7 knockdown in MSCs to restore proliferation and cytokine production in T-cells. These results suggest that IGFBP7 may act as a novel MSC-secreted immunomodulatory factor. |
| Databáze: | OpenAIRE |
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