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Mouse Sertoli Cells Inhibit Humoral-Based Immunity

Transplantation is used to treat many different diseases; however, without the use of immunosuppressants, which can be toxic to the patient, grafted tissue is rejected by the immune system. Humoral immune responses, particularly antibodies and complement, are significant components in rejection. Rem...

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Autores principales: Washburn, Rachel L., Kaur, Gurvinder, Dufour, Jannette M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656144/
https://www.ncbi.nlm.nih.gov/pubmed/36361551
http://dx.doi.org/10.3390/ijms232112760
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author Washburn, Rachel L.
Kaur, Gurvinder
Dufour, Jannette M.
author_facet Washburn, Rachel L.
Kaur, Gurvinder
Dufour, Jannette M.
author_sort Washburn, Rachel L.
collection PubMed
description Transplantation is used to treat many different diseases; however, without the use of immunosuppressants, which can be toxic to the patient, grafted tissue is rejected by the immune system. Humoral immune responses, particularly antibodies and complement, are significant components in rejection. Remarkably, Sertoli cells (SCs), immunoregulatory testicular cells, survive long-term after transplantation without immunosuppression. The objective of this study was to assess SC regulation of these humoral-based immune factors. Mouse SCs survived in vitro human complement (model of robust complement-mediated rejection) and survived in vivo as allografts with little-to-no antibody or complement fragment deposition. Microarray data and ELISA analyses identified at least 14 complement inhibitory proteins expressed by mouse SCs, which inhibit complement at multiple points. Interestingly, a mouse SC line (MSC-1), which was rejected by day 20 post transplantation, also survived in vitro human complement, showed limited deposition of antibodies and complement, and expressed complement inhibitors. Together this suggests that SC inhibition of complement-mediated killing is an important component of SC immune regulation. However, other mechanisms of SC immune modulation are also likely involved in SC graft survival. Identifying the mechanisms that SCs use to achieve extended survival as allografts could be utilized to improve graft survival.
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spelling pubmed-96561442022-11-15 Mouse Sertoli Cells Inhibit Humoral-Based Immunity Washburn, Rachel L. Kaur, Gurvinder Dufour, Jannette M. Int J Mol Sci Article Transplantation is used to treat many different diseases; however, without the use of immunosuppressants, which can be toxic to the patient, grafted tissue is rejected by the immune system. Humoral immune responses, particularly antibodies and complement, are significant components in rejection. Remarkably, Sertoli cells (SCs), immunoregulatory testicular cells, survive long-term after transplantation without immunosuppression. The objective of this study was to assess SC regulation of these humoral-based immune factors. Mouse SCs survived in vitro human complement (model of robust complement-mediated rejection) and survived in vivo as allografts with little-to-no antibody or complement fragment deposition. Microarray data and ELISA analyses identified at least 14 complement inhibitory proteins expressed by mouse SCs, which inhibit complement at multiple points. Interestingly, a mouse SC line (MSC-1), which was rejected by day 20 post transplantation, also survived in vitro human complement, showed limited deposition of antibodies and complement, and expressed complement inhibitors. Together this suggests that SC inhibition of complement-mediated killing is an important component of SC immune regulation. However, other mechanisms of SC immune modulation are also likely involved in SC graft survival. Identifying the mechanisms that SCs use to achieve extended survival as allografts could be utilized to improve graft survival. MDPI 2022-10-23 /pmc/articles/PMC9656144/ /pubmed/36361551 http://dx.doi.org/10.3390/ijms232112760 Text en © 2022 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.
Kaur, Gurvinder
Dufour, Jannette M.
Mouse Sertoli Cells Inhibit Humoral-Based Immunity
title Mouse Sertoli Cells Inhibit Humoral-Based Immunity
title_full Mouse Sertoli Cells Inhibit Humoral-Based Immunity
title_fullStr Mouse Sertoli Cells Inhibit Humoral-Based Immunity
title_full_unstemmed Mouse Sertoli Cells Inhibit Humoral-Based Immunity
title_short Mouse Sertoli Cells Inhibit Humoral-Based Immunity
title_sort mouse sertoli cells inhibit humoral-based immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656144/
https://www.ncbi.nlm.nih.gov/pubmed/36361551
http://dx.doi.org/10.3390/ijms232112760
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