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Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses

The participating signals and structures that enable primary immune cells migrating within dense tissues are not completely revealed until now. Especially in autoimmune diseases, mostly unknown mechanisms facilitate autoreactive immune cells to migrate to endogenous tissues, infiltrating and harming...

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Autores principales: Wiedemann, Carmen, Amann, Barbara, Degroote, Roxane L., Witte, Tanja, Deeg, Cornelia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076317/
https://www.ncbi.nlm.nih.gov/pubmed/32211402
http://dx.doi.org/10.3389/fcell.2020.00101
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author Wiedemann, Carmen
Amann, Barbara
Degroote, Roxane L.
Witte, Tanja
Deeg, Cornelia A.
author_facet Wiedemann, Carmen
Amann, Barbara
Degroote, Roxane L.
Witte, Tanja
Deeg, Cornelia A.
author_sort Wiedemann, Carmen
collection PubMed
description The participating signals and structures that enable primary immune cells migrating within dense tissues are not completely revealed until now. Especially in autoimmune diseases, mostly unknown mechanisms facilitate autoreactive immune cells to migrate to endogenous tissues, infiltrating and harming organ-specific structures. In order to gain deeper insights into the migratory behavior of primary autoreactive immune cells, we examined peripheral blood-derived lymphocytes (PBLs) of horses with equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis in humans. In this study, we used a three-dimensional collagen I hydrogel matrix and monitored live-cell migration of primary lymphocytes as a reaction to different chemoattractants such as fetal calf serum (FCS), cytokines interleukin-4 (IL-4), and interferon-γ (IFN-γ), and a specific uveitis autoantigen, cellular retinaldehyde binding protein (CRALBP). Through these experiments, we uncovered distinct differences between PBLs from ERU cases and PBLs from healthy animals, with significantly higher cell motility, cell speed, and straightness during migration of PBLs from ERU horses. Furthermore, we emphasized the significance of expression levels and cellular localization of septin 7, a membrane-interacting protein with decreased abundance in PBLs of autoimmune cases. To underline the importance of septin 7 expression changes and the possible contribution to migratory behavior in autoreactive immune cells, we used forchlorfenuron (FCF) as a reversible inhibitor of septin structures. FCF-treated cells showed more directed migration through dense tissue and revealed aberrant septin 7 and F-actin structures along with different protein distribution and translocalization of the latter, uncovered by immunochemistry. Hence, we propose that septin 7 and interacting molecules play a pivotal role in the organization and regulation of cell shaping and migration. With our findings, we contribute to gaining deeper insights into the migratory behavior and septin 7-dependent cytoskeletal reorganization of immune cells in organ-specific autoimmune diseases.
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spelling pubmed-70763172020-03-24 Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses Wiedemann, Carmen Amann, Barbara Degroote, Roxane L. Witte, Tanja Deeg, Cornelia A. Front Cell Dev Biol Cell and Developmental Biology The participating signals and structures that enable primary immune cells migrating within dense tissues are not completely revealed until now. Especially in autoimmune diseases, mostly unknown mechanisms facilitate autoreactive immune cells to migrate to endogenous tissues, infiltrating and harming organ-specific structures. In order to gain deeper insights into the migratory behavior of primary autoreactive immune cells, we examined peripheral blood-derived lymphocytes (PBLs) of horses with equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis in humans. In this study, we used a three-dimensional collagen I hydrogel matrix and monitored live-cell migration of primary lymphocytes as a reaction to different chemoattractants such as fetal calf serum (FCS), cytokines interleukin-4 (IL-4), and interferon-γ (IFN-γ), and a specific uveitis autoantigen, cellular retinaldehyde binding protein (CRALBP). Through these experiments, we uncovered distinct differences between PBLs from ERU cases and PBLs from healthy animals, with significantly higher cell motility, cell speed, and straightness during migration of PBLs from ERU horses. Furthermore, we emphasized the significance of expression levels and cellular localization of septin 7, a membrane-interacting protein with decreased abundance in PBLs of autoimmune cases. To underline the importance of septin 7 expression changes and the possible contribution to migratory behavior in autoreactive immune cells, we used forchlorfenuron (FCF) as a reversible inhibitor of septin structures. FCF-treated cells showed more directed migration through dense tissue and revealed aberrant septin 7 and F-actin structures along with different protein distribution and translocalization of the latter, uncovered by immunochemistry. Hence, we propose that septin 7 and interacting molecules play a pivotal role in the organization and regulation of cell shaping and migration. With our findings, we contribute to gaining deeper insights into the migratory behavior and septin 7-dependent cytoskeletal reorganization of immune cells in organ-specific autoimmune diseases. Frontiers Media S.A. 2020-03-10 /pmc/articles/PMC7076317/ /pubmed/32211402 http://dx.doi.org/10.3389/fcell.2020.00101 Text en Copyright © 2020 Wiedemann, Amann, Degroote, Witte and Deeg. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wiedemann, Carmen
Amann, Barbara
Degroote, Roxane L.
Witte, Tanja
Deeg, Cornelia A.
Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses
title Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses
title_full Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses
title_fullStr Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses
title_full_unstemmed Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses
title_short Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses
title_sort aberrant migratory behavior of immune cells in recurrent autoimmune uveitis in horses
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076317/
https://www.ncbi.nlm.nih.gov/pubmed/32211402
http://dx.doi.org/10.3389/fcell.2020.00101
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