The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival
The complement system is an important component of transplant rejection. Sertoli cells, an immune regulatory testicular cell, survive long-term when transplanted across immunological barriers; thus, understanding the mechanisms behind this unique survival would be of great benefit to the transplanta...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/1890 |
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| author | Rachel L. Washburn Dalia Martinez-Marin Ksenija Korać Tyler Sniegowski Alexis R. Rodriguez Beverly S. Chilton Taylor Hibler Kevin Pruitt Yangzom D. Bhutia Jannette M. Dufour |
| author_facet | Rachel L. Washburn Dalia Martinez-Marin Ksenija Korać Tyler Sniegowski Alexis R. Rodriguez Beverly S. Chilton Taylor Hibler Kevin Pruitt Yangzom D. Bhutia Jannette M. Dufour |
| author_sort | Rachel L. Washburn |
| collection | DOAJ |
| description | The complement system is an important component of transplant rejection. Sertoli cells, an immune regulatory testicular cell, survive long-term when transplanted across immunological barriers; thus, understanding the mechanisms behind this unique survival would be of great benefit to the transplantation field. This study focused on Sertoli cell inhibition of complement as relevant in xenotransplantation. Neonatal pig Sertoli cells (NPSCs) survived activated human complement in vitro while neonatal pig islet (NPI) aggregates and pig aortic endothelial cell (PAEC) survival were diminished to about 65% and 12%, respectively. PAECs cultured in NPSC-conditioned media and human complement demonstrated a 200% increase in survival suggesting that NPSCs secrete complement-inhibiting substances that confer protection. Bioinformatic and molecular analyses identified 21 complement inhibitors expressed by NPSCs with several significantly increased in NPSCs compared to NPIs or PAECs. Lastly, RNA sequencing revealed that NPSCs express 25 other complement factors including cascade components and receptors. Overall, this study identified the most comprehensive Sertoli cell complement signature to date and indicates that the expression of a variety of complement inhibitors ensures a proper regulation of complement through redundant inhibition points. Understanding the regulation of the complement system should be further investigated for extending xenograft viability. |
| first_indexed | 2024-03-11T09:42:27Z |
| format | Article |
| id | doaj.art-02ddee60c450489a9b7686383e484217 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:27Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-02ddee60c450489a9b7686383e4842172023-11-16T16:49:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243189010.3390/ijms24031890The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft SurvivalRachel L. Washburn0Dalia Martinez-Marin1Ksenija Korać2Tyler Sniegowski3Alexis R. Rodriguez4Beverly S. Chilton5Taylor Hibler6Kevin Pruitt7Yangzom D. Bhutia8Jannette M. Dufour9Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Immunology and Molecular Microbiology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79404, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USADepartment of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USAThe complement system is an important component of transplant rejection. Sertoli cells, an immune regulatory testicular cell, survive long-term when transplanted across immunological barriers; thus, understanding the mechanisms behind this unique survival would be of great benefit to the transplantation field. This study focused on Sertoli cell inhibition of complement as relevant in xenotransplantation. Neonatal pig Sertoli cells (NPSCs) survived activated human complement in vitro while neonatal pig islet (NPI) aggregates and pig aortic endothelial cell (PAEC) survival were diminished to about 65% and 12%, respectively. PAECs cultured in NPSC-conditioned media and human complement demonstrated a 200% increase in survival suggesting that NPSCs secrete complement-inhibiting substances that confer protection. Bioinformatic and molecular analyses identified 21 complement inhibitors expressed by NPSCs with several significantly increased in NPSCs compared to NPIs or PAECs. Lastly, RNA sequencing revealed that NPSCs express 25 other complement factors including cascade components and receptors. Overall, this study identified the most comprehensive Sertoli cell complement signature to date and indicates that the expression of a variety of complement inhibitors ensures a proper regulation of complement through redundant inhibition points. Understanding the regulation of the complement system should be further investigated for extending xenograft viability.https://www.mdpi.com/1422-0067/24/3/1890Sertoli cellsimmune regulationcomplementtransplantationxenografts |
| spellingShingle | Rachel L. Washburn Dalia Martinez-Marin Ksenija Korać Tyler Sniegowski Alexis R. Rodriguez Beverly S. Chilton Taylor Hibler Kevin Pruitt Yangzom D. Bhutia Jannette M. Dufour The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival International Journal of Molecular Sciences Sertoli cells immune regulation complement transplantation xenografts |
| title | The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival |
| title_full | The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival |
| title_fullStr | The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival |
| title_full_unstemmed | The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival |
| title_short | The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival |
| title_sort | sertoli cell complement signature a suspected mechanism in xenograft survival |
| topic | Sertoli cells immune regulation complement transplantation xenografts |
| url | https://www.mdpi.com/1422-0067/24/3/1890 |
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