Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses.
Abstract: 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.
Copyright © 2020 Wiedemann, Amann, Degroote, Witte and Deeg.
Publication Date: 2020-03-10 PubMed ID: 32211402PubMed Central: PMC7076317DOI: 10.3389/fcell.2020.00101Google Scholar: Lookup
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Summary
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The research article is about understanding why immune cells behave abnormally in recurring autoimmune uveitis in horses. It aims to uncover the mechanisms that enable immune cells to migrate to tissues, infiltrating and damaging specific organs, focusing on peripheral blood-derived lymphocytes (PBLs) from horses affected by equine recurrent uveitis (ERU).
Exploring Migratory Behavior of Immune Cells
- The team conducted an in-depth examination of peripheral blood-derived lymphocytes (PBLs) from horses with equine recurrent uveitis (ERU), an equivalent to autoimmune uveitis in humans. This was performed to understand the migration patterns of autoreactive immune cells, which are cells that erroneously recognize the body’s tissues as harmful and attack them.
- A three-dimensional collagen I hydrogel matrix was used to monitor live-cell migration of primary lymphocytes and their 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).
Findings and Observations
- The study found distinct differences between the behavior of PBLs from horses affected by ERU and those from healthy animals. The former category displayed higher cell motility, cell speed, and straightness during migration.
- Another important finding was related to septin 7, a membrane-interacting protein. The researchers noted a decrease in the expression levels and cellular localization of this protein in the PBLs of horses with autoimmune issues, compared to the healthy ones.
Role of Septin 7
- To further understand septin 7’s role and its impact on cell migration, the researchers used forchlorfenuron (FCF), a reversible inhibitor. They found that this treatment resulted in directed migration through dense tissue and caused irregularities in septin 7 and F-actin structures.
- These changes in septin 7 and F-actin, along with different protein distribution patterns, were revealed through immunohistochemistry, a technique used to visualize specific components of cells.
- As a result, septin 7 and interacting molecules appear crucial in the organization and regulation of cell shaping and migration, thus giving this protein more research attention in the context of autoimmune diseases.
Value and Relevance of the Study
- The study lays the groundwork for gaining a deeper understanding of immune cell migration and the role of the protein septin 7 in these processes, specifically in cases of organ-specific autoimmune diseases.
- The findings could be crucial in the development of therapies targeting the dysfunctional migration behavior of autoreactive immune cells in autoimmune diseases.
Cite This Article
APA
Wiedemann C, Amann B, Degroote RL, Witte T, Deeg CA.
(2020).
Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses.
Front Cell Dev Biol, 8, 101.
https://doi.org/10.3389/fcell.2020.00101 Publication
Researcher Affiliations
- Chair of Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
- Chair of Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
- Chair of Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
- Faculty of Veterinary Medicine, Equine Hospital, LMU Munich, Munich, Germany.
- Chair of Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
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Citations
This article has been cited 6 times.- Sprenzel CJ, Amann B, Deeg CA, Degroote RL. Glycan Signatures on Neutrophils in an Equine Model for Autoimmune Uveitis. Biomolecules 2025 Oct 12;15(10).
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