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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916409/ https://www.ncbi.nlm.nih.gov/pubmed/36768217 http://dx.doi.org/10.3390/ijms24031890 |
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author | Washburn, Rachel L. Martinez-Marin, Dalia Korać, Ksenija Sniegowski, Tyler Rodriguez, Alexis R. Chilton, Beverly S. Hibler, Taylor Pruitt, Kevin Bhutia, Yangzom D. Dufour, Jannette M. |
author_facet | Washburn, Rachel L. Martinez-Marin, Dalia Korać, Ksenija Sniegowski, Tyler Rodriguez, Alexis R. Chilton, Beverly S. Hibler, Taylor Pruitt, Kevin Bhutia, Yangzom D. Dufour, Jannette M. |
author_sort | Washburn, Rachel L. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9916409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99164092023-02-11 The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival Washburn, Rachel L. Martinez-Marin, Dalia Korać, Ksenija Sniegowski, Tyler Rodriguez, Alexis R. Chilton, Beverly S. Hibler, Taylor Pruitt, Kevin Bhutia, Yangzom D. Dufour, Jannette M. Int J Mol Sci Article 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. MDPI 2023-01-18 /pmc/articles/PMC9916409/ /pubmed/36768217 http://dx.doi.org/10.3390/ijms24031890 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Washburn, Rachel L. Martinez-Marin, Dalia Korać, Ksenija Sniegowski, Tyler Rodriguez, Alexis R. Chilton, Beverly S. Hibler, Taylor Pruitt, Kevin Bhutia, Yangzom D. Dufour, Jannette M. The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916409/ https://www.ncbi.nlm.nih.gov/pubmed/36768217 http://dx.doi.org/10.3390/ijms24031890 |
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