Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation
Background aims: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory...
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| Format: | Article |
| Language: | English |
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Elsevier
2016
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| Online Access: | http://psasir.upm.edu.my/id/eprint/54461/1/Human%20mesenchymal%20stromal%20cells%20modulate%20T-cell%20immune%20response%20via%20transcriptomic%20regulation.pdf |
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| author | Vellasamy, Shalini Tong, Chih Kong Azhar, Nur Atiqah Kodiappan, Radha Chan, Soon Choy Veerakumarasivam, Abhi Ramasamy, Rajesh |
| author_facet | Vellasamy, Shalini Tong, Chih Kong Azhar, Nur Atiqah Kodiappan, Radha Chan, Soon Choy Veerakumarasivam, Abhi Ramasamy, Rajesh |
| author_sort | Vellasamy, Shalini |
| collection | UPM |
| description | Background aims: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated. Methods: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord–derived MSCs (UC-MSCs) on activated T cells. Results: In the presence of UC-MSCs, the proliferation of activated T cells was suppressed in a dose-depended manner by cell-to-cell contact mode via an active cell-cycle arrest at the G0/G1 phase of the cell cycle. The microarray analysis revealed that particularly, IFNG, CXCL9, IL2, IL2RA and CCND3 genes were down-regulated, whereas IL11, VSIG4, GFA1, TIMP3 and BBC3 genes were up-regulated by UC-MSCs. The dysregulated gene clusters associated with immune-response-related ontologies, namely, lymphocyte proliferation or activation, apoptosis and cell cycle, were further analyzed. Conclusions: Among the nine canonical pathways identified, three pathways (namely T-helper cell differentiation, cyclins and cell cycle regulation, and gap/tight junction signalling pathways) were highly enriched with these dysregulated genes. The pathways represent putative molecular pathways through which UC-MSCs elicit immunosuppressive activity toward activated T cells. This study provides a global snapshot of gene networks and pathways that contribute to the ability of UC-MSCs to suppress activated T cells. |
| first_indexed | 2024-03-06T09:20:44Z |
| format | Article |
| id | upm.eprints-54461 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:20:44Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-544612018-03-19T07:56:17Z http://psasir.upm.edu.my/id/eprint/54461/ Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation Vellasamy, Shalini Tong, Chih Kong Azhar, Nur Atiqah Kodiappan, Radha Chan, Soon Choy Veerakumarasivam, Abhi Ramasamy, Rajesh Background aims: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated. Methods: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord–derived MSCs (UC-MSCs) on activated T cells. Results: In the presence of UC-MSCs, the proliferation of activated T cells was suppressed in a dose-depended manner by cell-to-cell contact mode via an active cell-cycle arrest at the G0/G1 phase of the cell cycle. The microarray analysis revealed that particularly, IFNG, CXCL9, IL2, IL2RA and CCND3 genes were down-regulated, whereas IL11, VSIG4, GFA1, TIMP3 and BBC3 genes were up-regulated by UC-MSCs. The dysregulated gene clusters associated with immune-response-related ontologies, namely, lymphocyte proliferation or activation, apoptosis and cell cycle, were further analyzed. Conclusions: Among the nine canonical pathways identified, three pathways (namely T-helper cell differentiation, cyclins and cell cycle regulation, and gap/tight junction signalling pathways) were highly enriched with these dysregulated genes. The pathways represent putative molecular pathways through which UC-MSCs elicit immunosuppressive activity toward activated T cells. This study provides a global snapshot of gene networks and pathways that contribute to the ability of UC-MSCs to suppress activated T cells. Elsevier 2016-10 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/54461/1/Human%20mesenchymal%20stromal%20cells%20modulate%20T-cell%20immune%20response%20via%20transcriptomic%20regulation.pdf Vellasamy, Shalini and Tong, Chih Kong and Azhar, Nur Atiqah and Kodiappan, Radha and Chan, Soon Choy and Veerakumarasivam, Abhi and Ramasamy, Rajesh (2016) Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation. Cytotherapy, 18 (10). pp. 1270-1283. ISSN 1465-3249; ESSN: 1477-2566 https://www.sciencedirect.com/science/article/pii/S1465324916304510?via%3Dihub Cell-cycle arrest; Gene expression; Immunomodulation; Mesenchymal stromal cells; T cells 10.1016/j.jcyt.2016.06.017 |
| spellingShingle | Cell-cycle arrest; Gene expression; Immunomodulation; Mesenchymal stromal cells; T cells Vellasamy, Shalini Tong, Chih Kong Azhar, Nur Atiqah Kodiappan, Radha Chan, Soon Choy Veerakumarasivam, Abhi Ramasamy, Rajesh Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation |
| title | Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation |
| title_full | Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation |
| title_fullStr | Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation |
| title_full_unstemmed | Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation |
| title_short | Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation |
| title_sort | human mesenchymal stromal cells modulate t cell immune response via transcriptomic regulation |
| topic | Cell-cycle arrest; Gene expression; Immunomodulation; Mesenchymal stromal cells; T cells |
| url | http://psasir.upm.edu.my/id/eprint/54461/1/Human%20mesenchymal%20stromal%20cells%20modulate%20T-cell%20immune%20response%20via%20transcriptomic%20regulation.pdf |
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