Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways
Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyalu...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2015/614297 |
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| _version_ | 1832552135720435712 |
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| author | Shannon M. Ruppert Ben A. Falk S. Alice Long Paul L. Bollyky |
| author_facet | Shannon M. Ruppert Ben A. Falk S. Alice Long Paul L. Bollyky |
| author_sort | Shannon M. Ruppert |
| collection | DOAJ |
| description | Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA. |
| format | Article |
| id | doaj-art-11307a7e9bfa4127ae06c05d15f49d26 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-11307a7e9bfa4127ae06c05d15f49d262025-02-03T05:59:20ZengWileyInternational Journal of Cell Biology1687-88761687-88842015-01-01201510.1155/2015/614297614297Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling PathwaysShannon M. Ruppert0Ben A. Falk1S. Alice Long2Paul L. Bollyky3Division of Infectious Diseases and Geographic Medicine, Department of Medicine, 300 Pasteur Drive, Stanford University School of Medicine, Stanford, CA 94305-5107, USADivision of Infectious Diseases and Geographic Medicine, Department of Medicine, 300 Pasteur Drive, Stanford University School of Medicine, Stanford, CA 94305-5107, USABenaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101, USADivision of Infectious Diseases and Geographic Medicine, Department of Medicine, 300 Pasteur Drive, Stanford University School of Medicine, Stanford, CA 94305-5107, USACyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA.http://dx.doi.org/10.1155/2015/614297 |
| spellingShingle | Shannon M. Ruppert Ben A. Falk S. Alice Long Paul L. Bollyky Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways International Journal of Cell Biology |
| title | Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways |
| title_full | Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways |
| title_fullStr | Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways |
| title_full_unstemmed | Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways |
| title_short | Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways |
| title_sort | regulatory t cells resist cyclosporine induced cell death via cd44 mediated signaling pathways |
| url | http://dx.doi.org/10.1155/2015/614297 |
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