Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells
Abstract Mesenchymal stem/stromal cells can modulate the effector immune cells especially T lymphocytes. Due to this important feature, they can regulate the development of a variety of disorders including inflammatory and autoimmune disorders, cancers, and transplantation outcomes. One of the most...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-020-02057-z |
| _version_ | 1818329676984090624 |
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| author | Sina Naserian Sara Shamdani Nassim Arouche Georges Uzan |
| author_facet | Sina Naserian Sara Shamdani Nassim Arouche Georges Uzan |
| author_sort | Sina Naserian |
| collection | DOAJ |
| description | Abstract Mesenchymal stem/stromal cells can modulate the effector immune cells especially T lymphocytes. Due to this important feature, they can regulate the development of a variety of disorders including inflammatory and autoimmune disorders, cancers, and transplantation outcomes. One of the most important MSC immunoregulatory functions is their capacity to convert conventional T cells into regulatory T cells. Several mechanisms, mostly related to MSCs but not T cells, have been shown essential for this aspect. The inflammatory microenvironment majorly caused by pro-inflammatory cytokines has been demonstrated to govern the direction of the immune response. In this respect, we have recently revealed that the TNFα-TNFR2 signaling controls several aspects of MSC immunomodulatory properties including their ability to suppress T cells and their conversion towards Foxp3-expressing Tregs. Here in this work, we have looked from another angle by investigating the impact of TNFR2 expression by T cells on their ability to be converted to suppressive Tregs by MSCs. We showed that unlike WT-T cells, their TNFR2 KO counterparts are remarkably less able to convert into Foxp3+ and Foxp3− Tregs. Furthermore, TNFR2 blockade diminished the anti-inflammatory cytokine secretion by iTregs and consequently resulted in less T cell immunosuppression. This work is the first evidence of the crucial association of TNFR2 expression by T cells with their iTreg conversion capacity by MSCs. It strengthens once more the potential of anti-TNFR2 administration for a strong and effective interference with the immunosuppression exerted by TNFR2-expressing cells. |
| first_indexed | 2024-12-13T12:51:51Z |
| format | Article |
| id | doaj.art-109282e48d5f4ad19df2dadcd42b8f32 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T12:51:51Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-109282e48d5f4ad19df2dadcd42b8f322022-12-21T23:45:18ZengBMCStem Cell Research & Therapy1757-65122020-12-011111710.1186/s13287-020-02057-zRegulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cellsSina Naserian0Sara Shamdani1Nassim Arouche2Georges Uzan3INSERM UMR-S-MD 1197, Hôpital Paul BrousseINSERM UMR-S-MD 1197, Hôpital Paul BrousseINSERM UMR-S-MD 1197, Hôpital Paul BrousseINSERM UMR-S-MD 1197, Hôpital Paul BrousseAbstract Mesenchymal stem/stromal cells can modulate the effector immune cells especially T lymphocytes. Due to this important feature, they can regulate the development of a variety of disorders including inflammatory and autoimmune disorders, cancers, and transplantation outcomes. One of the most important MSC immunoregulatory functions is their capacity to convert conventional T cells into regulatory T cells. Several mechanisms, mostly related to MSCs but not T cells, have been shown essential for this aspect. The inflammatory microenvironment majorly caused by pro-inflammatory cytokines has been demonstrated to govern the direction of the immune response. In this respect, we have recently revealed that the TNFα-TNFR2 signaling controls several aspects of MSC immunomodulatory properties including their ability to suppress T cells and their conversion towards Foxp3-expressing Tregs. Here in this work, we have looked from another angle by investigating the impact of TNFR2 expression by T cells on their ability to be converted to suppressive Tregs by MSCs. We showed that unlike WT-T cells, their TNFR2 KO counterparts are remarkably less able to convert into Foxp3+ and Foxp3− Tregs. Furthermore, TNFR2 blockade diminished the anti-inflammatory cytokine secretion by iTregs and consequently resulted in less T cell immunosuppression. This work is the first evidence of the crucial association of TNFR2 expression by T cells with their iTreg conversion capacity by MSCs. It strengthens once more the potential of anti-TNFR2 administration for a strong and effective interference with the immunosuppression exerted by TNFR2-expressing cells.https://doi.org/10.1186/s13287-020-02057-zMesenchymal stem cellsRegulatory T cellsTNF-TNFR2 signaling pathwayImmune checkpointImmunosuppressionImmunoregulation |
| spellingShingle | Sina Naserian Sara Shamdani Nassim Arouche Georges Uzan Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells Stem Cell Research & Therapy Mesenchymal stem cells Regulatory T cells TNF-TNFR2 signaling pathway Immune checkpoint Immunosuppression Immunoregulation |
| title | Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells |
| title_full | Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells |
| title_fullStr | Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells |
| title_full_unstemmed | Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells |
| title_short | Regulatory T cell induction by mesenchymal stem cells depends on the expression of TNFR2 by T cells |
| title_sort | regulatory t cell induction by mesenchymal stem cells depends on the expression of tnfr2 by t cells |
| topic | Mesenchymal stem cells Regulatory T cells TNF-TNFR2 signaling pathway Immune checkpoint Immunosuppression Immunoregulation |
| url | https://doi.org/10.1186/s13287-020-02057-z |
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