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Formin like 1 expression is increased on CD4+ T lymphocytes in spontaneous autoimmune uveitis.
Abstract: The membrane protein expression repertoire of cells changes in course of activation. In equine recurrent uveitis (ERU), a spontaneous autoimmune disease in horses with relapsing and ultimately blinding inner eye inflammation, CD4+ T lymphocytes are the crucial pathogenic cells activated in the periphery directly prior to an inflammatory episode. In order to find relevant changes in the membrane proteome associated to disease, we sorted CD4+ lymphocytes and compared protein abundance from the generated proteome datasets of both healthy horses and ERU cases. We detected formin like 1, a key player in actin dependent cellular processes such as phagocytosis, cell adhesion and cell migration, with significantly higher abundance in the CD4+ cell membrane proteome of horses with ERU. In transmigration experiments, we demonstrated higher migration rate of cells originating from diseased animals connecting formin like 1 to the migratory ability of cells. These findings are the first description of formin like 1 in association to processes involved in migration of inflammatory CD4+ T cells across the blood-retinal barrier in a spontaneous ocular autoimmune disease and suggest formin like 1 to play a role in the molecular mechanisms of ERU disease pathogenesis. Data are available via ProteomeXchange with identifier PXD005384. This comparative proteomic study of membrane proteins of CD4+ T cells identified a novel protein, formin like 1, with expression on the plasma cell membrane of equine CD4+ T cells and a significant change of abundance on CD4+ T cells of horses with a spontaneous autoimmune disease. Functional studies in a cell culture model for transmigration at the blood-retinal barrier (BRB) unraveled a strong impact of formin like 1 on migratory processes of CD4+ T cells across the BRB, a key event in uveitis pathogenesis. These findings provide novel knowledge about changes in the CD4+ immune cell membrane proteome in a spontaneously and naturally occurring autoimmune disease in horses with high relevance for veterinary medicine. Additionally, this model has proven translational quality for human medicine and provides novel proteomic information on autoimmune uveitis in man.
Copyright © 2017 Elsevier B.V. All rights reserved.
Publication Date: 2017-01-03 PubMed ID: 28057602DOI: 10.1016/j.jprot.2016.12.015Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study discovers that formin like 1, a protein playing a key role in cellular processes, has higher abundance on CD4+ immune cells in horses with equine recurrent uveitis (ERU), a spontaneous autoimmune disease causing recurring and ultimately blinding eye inflammation. This has implications for both veterinary and human medicine.
Research Background
- The research focuses on equine recurrent uveitis (ERU), an autoimmune disease in horses which causes repeated and eventually blinding inner-eye inflammation.
- In ERU, CD4+ T lymphocytes, a type of white blood cell, are the main pathogenic cells activated just before an inflammatory episode.
- This study sought to identify changes in the surface protein expression of these cells related to the disease.
Methodology
- The researchers compared protein abundance levels in isolated CD4+ lymphocytes from healthy horses and those with ERU.
- They used the data from their proteome datasets – a comprehensive list of the proteins present in the cells – to identify any significant changes.
Findings
- The comparison revealed a significantly higher abundance of the protein formin like 1 in the membrane proteome of CD4+ cells from horses with ERU.
- This protein is known to be involved in actin-dependent cellular processes including phagocytosis, cell adhesion, and cell migration.
- Connection was found between formin like 1 and the higher migration rate of cells coming from diseased horses in transmigration experiments, implying the protein’s role in cell migration.
- This was the first description of formin like 1 associated with migration of inflammatory CD4+ T cells across the blood-retinal barrier in an ocular autoimmune disease.
Conclusion
- The study suggests that formin like 1 plays a role in the molecular mechanisms of ERU disease pathogenesis.
- The research may provide novel information on autoimmune uveitis in humans as well, given the translational quality of this model for human medicine.
Cite This Article
APA
Degroote RL, Uhl PB, Amann B, Krackhardt AM, Ueffing M, Hauck SM, Deeg CA.
(2017).
Formin like 1 expression is increased on CD4+ T lymphocytes in spontaneous autoimmune uveitis.
J Proteomics, 154, 102-108.
https://doi.org/10.1016/j.jprot.2016.12.015 Publication
Researcher Affiliations
- Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, Germany.
- Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, Germany.
- Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, Germany.
- III. Medical Department, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
- Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 80939 Munich, Germany; Medical Proteome Center, Institute for Ophthalmic Research, Eberhard Karls Universität Tübingen, 72074 Tuebingen, Germany.
- Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 80939 Munich, Germany.
- Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, Germany; Experimental Ophthalmology, Philipps-Universität Marburg, 35033 Marburg, Germany. Electronic address: Cornelia.Deeg@uni-marburg.de.
MeSH Terms
- Animals
- Autoimmune Diseases / etiology
- Autoimmune Diseases / pathology
- Autoimmune Diseases / veterinary
- Blood-Retinal Barrier / pathology
- CD4-Positive T-Lymphocytes / chemistry
- CD4-Positive T-Lymphocytes / pathology
- Cell Movement / immunology
- Cytoskeletal Proteins / metabolism
- Horse Diseases / diagnosis
- Horse Diseases / etiology
- Horse Diseases / pathology
- Horses / immunology
- Membrane Proteins / analysis
- Proteome / analysis
- Proteomics / methods
- Uveitis / etiology
- Uveitis / pathology
- Uveitis / veterinary
Citations
This article has been cited 12 times.- Narasimha RB, Shreya S, Jayabal VA, Yadav V, Rath PK, Mishra BP, Kancharla S, Kolli P, Mandadapu G, Kumar S, Mohanty AK, Jena MK. Stem Cell Therapy for Diseases of Livestock Animals: An In-Depth Review. Vet Sci 2025 Jan 17;12(1).
- Xiao J, Zhao C, Cheng G, Song H, Zhang Y, Zhang M. Multiple cytokine analysis of aqueous humor in uveitis with or without secondary glaucoma. BMC Ophthalmol 2024 Oct 15;24(1):451.
- Stamoula E, Sarantidi E, Dimakopoulos V, Ainatzoglou A, Dardalas I, Papazisis G, Kontopoulou K, Anagnostopoulos AK. Serum Proteome Signatures of Anti-SARS-CoV-2 Vaccinated Healthcare Workers in Greece Associated with Their Prior Infection Status. Int J Mol Sci 2022 Sep 5;23(17).
- Sun J, Zhong X, Fu X, Miller H, Lee P, Yu B, Liu C. The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes. Front Immunol 2022;13:799309.
- Wollanke B, Gerhards H, Ackermann K. Infectious Uveitis in Horses and New Insights in Its Leptospiral Biofilm-Related Pathogenesis. Microorganisms 2022 Feb 7;10(2).
- Barfüßer C, Wiedemann C, Hoffmann ALC, Hirmer S, Deeg CA. Altered Metabolic Phenotype of Immune Cells in a Spontaneous Autoimmune Uveitis Model. Front Immunol 2021;12:601619.
- Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
- Thompson SB, Sandor AM, Lui V, Chung JW, Waldman MM, Long RA, Estin ML, Matsuda JL, Friedman RS, Jacobelli J. Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity. Elife 2020 Jun 8;9.
- Wiedemann C, Amann B, Degroote RL, Witte T, Deeg CA. Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses. Front Cell Dev Biol 2020;8:101.
- Degroote RL, Weigand M, Hauck SM, Deeg CA. IL8 and PMA Trigger the Regulation of Different Biological Processes in Granulocyte Activation. Front Immunol 2019;10:3064.
- Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro. Vet Ophthalmol 2020 Jan;23(1):160-170.
- Velez G, Tang PH, Cabral T, Cho GY, Machlab DA, Tsang SH, Bassuk AG, Mahajan VB. Personalized Proteomics for Precision Health: Identifying Biomarkers of Vitreoretinal Disease. Transl Vis Sci Technol 2018 Sep;7(5):12.
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