Cargando…
Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro
Equine recurrent uveitis (ERU) is an immune‐mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many spe...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980227/ https://www.ncbi.nlm.nih.gov/pubmed/31441218 http://dx.doi.org/10.1111/vop.12704 |
_version_ | 1783490941481385984 |
---|---|
author | Saldinger, Laurel K. Nelson, Seldy G. Bellone, Rebecca R. Lassaline, Mary Mack, Maura Walker, Naomi J. Borjesson, Dori L. |
author_facet | Saldinger, Laurel K. Nelson, Seldy G. Bellone, Rebecca R. Lassaline, Mary Mack, Maura Walker, Naomi J. Borjesson, Dori L. |
author_sort | Saldinger, Laurel K. |
collection | PubMed |
description | Equine recurrent uveitis (ERU) is an immune‐mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T‐cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T‐cell phenotype. Adipose‐derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4(+) T‐cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T‐cells and B‐cells in horses with ERU were similar to normal horses. However, CD4(+) T‐cells from horses with ERU expressed higher amounts of IFNγ indicating a pro‐inflammatory Th1 phenotype. When co‐incubated with MSCs, activated CD4(+) T‐cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell‐cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4(+) T‐cell activation phenotype through a combination of cell‐cell contact and prostaglandin signaling. |
format | Online Article Text |
id | pubmed-6980227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69802272020-02-10 Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro Saldinger, Laurel K. Nelson, Seldy G. Bellone, Rebecca R. Lassaline, Mary Mack, Maura Walker, Naomi J. Borjesson, Dori L. Vet Ophthalmol Original Articles Equine recurrent uveitis (ERU) is an immune‐mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T‐cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T‐cell phenotype. Adipose‐derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4(+) T‐cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T‐cells and B‐cells in horses with ERU were similar to normal horses. However, CD4(+) T‐cells from horses with ERU expressed higher amounts of IFNγ indicating a pro‐inflammatory Th1 phenotype. When co‐incubated with MSCs, activated CD4(+) T‐cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell‐cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4(+) T‐cell activation phenotype through a combination of cell‐cell contact and prostaglandin signaling. John Wiley and Sons Inc. 2019-08-22 2020-01 /pmc/articles/PMC6980227/ /pubmed/31441218 http://dx.doi.org/10.1111/vop.12704 Text en © 2019 The Authors. Veterinary Ophthalmology published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Ophthalmologists This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Saldinger, Laurel K. Nelson, Seldy G. Bellone, Rebecca R. Lassaline, Mary Mack, Maura Walker, Naomi J. Borjesson, Dori L. Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
title | Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
title_full | Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
title_fullStr | Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
title_full_unstemmed | Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
title_short | Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
title_sort | horses with equine recurrent uveitis have an activated cd4+ t‐cell phenotype that can be modulated by mesenchymal stem cells in vitro |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980227/ https://www.ncbi.nlm.nih.gov/pubmed/31441218 http://dx.doi.org/10.1111/vop.12704 |
work_keys_str_mv | AT saldingerlaurelk horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro AT nelsonseldyg horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro AT bellonerebeccar horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro AT lassalinemary horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro AT mackmaura horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro AT walkernaomij horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro AT borjessondoril horseswithequinerecurrentuveitishaveanactivatedcd4tcellphenotypethatcanbemodulatedbymesenchymalstemcellsinvitro |