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Journal of proteome research2013; 12(12); 5812-5819; doi: 10.1021/pr400837f

Expression changes and novel interaction partners of talin 1 in effector cells of autoimmune uveitis.

Abstract: Autoimmune uveitis is characterized by crossing of blood-retinal barrier (BRB) by autoaggressive immune cells. Equine recurrent uveitis (ERU) is a valuable spontaneous model for autoimmune uveitis and analyses of differentially expressed proteins in ERU unraveled changed protein clusters in target tissues and immune system. Healthy eyes are devoid of leukocytes. In ERU, however, leukocytes enter the inner eye and subsequently destroy it. Molecular mechanisms enabling cell migration through BRB still remain elusive. Previously, we detected decreased talin 1 expression in blood-derived granulocytes of ERU cases, linking the innate immune system to ERU. Because changes in leukocyte protein expression pattern may play a role in pathological abnormalities leading to migration ability, we aimed at identifying interactors of talin 1 in leukocytes with immunoprecipitation, followed by LC-MS/MS for candidate identification. This enabled us to identify CD90 (Thy1) as novel interactor of talin 1 besides several other interactors. In blood-derived granulocytes from healthy individuals, CD90 was highly abundant and significantly reduced in ERU, especially in effector cells. Connection between talin 1 and CD90 and their expression differences in inflammation is an interesting novel finding allowing deeper insight into immune response of innate immune system and granulocyte migration ability in this organ-specific autoimmune disease.
Publication Date: 2013-11-06 PubMed ID: 24144192DOI: 10.1021/pr400837fGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research paper is about identifying new interaction partners of a protein called talin 1, specifically in the context of autoimmune uveitis (an inflammation of the eye often linked to autoimmune diseases), by using the naturally occurring model of the disease in horses.

Research Context

  • The researchers focused on autoimmune uveitis, a type of inflammation of the eye that occurs when the immune system attacks the body’s own cells. This condition is often characterized by the blood-retinal barrier (BRB) being crossed by aggressive immune cells.
  • The study used equine recurrent uveitis (ERU) as a spontaneous model for studying the condition. ERU is a recurrent inflammation of the uveal tract in horses that shares many clinical and pathological similarities with human autoimmune uveitis.
  • In healthy eyes, there are typically no leukocytes (white blood cells involved in protecting the body against both infectious disease and foreign invaders). However, in ERU, leukocytes infiltrate the inner eye, causing destruction.

Research Aim and Method

  • The researchers aimed to uncover the molecular mechanisms that allow leukocytes to cross the BRB. Specifically, they looked at talin 1, a protein they previously found to be expressed less in the blood-derived granulocytes (a type of white blood cell) of horses with ERU.
  • They hypothesized that changes in the protein expression pattern of leukocytes might contribute to the ability of these cells to migrate, a key pathological feature of ERU.
  • To identify proteins that interact with talin 1 in leukocytes, they used a technique called immunoprecipitation, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS), a method used for identifying and quantifying proteins.

Key Findings

  • The researchers identified a new interaction partner of talin 1: CD90, also known as Thy1. This protein was found to be highly abundant in granulocytes from healthy individuals but significantly reduced in ERU, especially in effector cells.
  • They also identified several other proteins that interact with talin 1 in leukocytes although they did not elaborate on these in the abstract.
  • The study points to a connection between talin 1 and CD90 and their differential expression during inflammation. This findings provide a deeper understanding of the immune response in ERU, particularly in relation to the migration ability of granulocytes.

Implications

  • This research offers new insights into the mechanisms that underpin leukocyte migration in autoimmune uveitis. The identification of new interaction partners of talin 1, like CD90, could potentially open up novel avenues for the development of therapies targeting these proteins.
  • The study also underscores the use of equine models in studying human autoimmune uveitis, which could be a promising approach in future research.

Cite This Article

APA
Degroote RL, Hauck SM, Treutlein G, Amann B, Fröhlich KJ, Kremmer E, Merl J, Stangassinger M, Ueffing M, Deeg CA. (2013). Expression changes and novel interaction partners of talin 1 in effector cells of autoimmune uveitis. J Proteome Res, 12(12), 5812-5819. https://doi.org/10.1021/pr400837f

Publication

ISSN: 1535-3907
NlmUniqueID: 101128775
Country: United States
Language: English
Volume: 12
Issue: 12
Pages: 5812-5819

Researcher Affiliations

Degroote, Roxane L
  • Institute of Animal Physiology, Department of Veterinary Sciences and ‡Clinic of Small Animal Medicine, Center of Clinical Veterinary Medicine, LMU Munich , Veterinaerstr. 13, D-80539 Munich, Germany.
Hauck, Stefanie M
    Treutlein, Gudrun
      Amann, Barbara
        Fröhlich, Kristina J H
          Kremmer, Elisabeth
            Merl, Juliane
              Stangassinger, Manfred
                Ueffing, Marius
                  Deeg, Cornelia A

                    MeSH Terms

                    • Animals
                    • Autoantibodies / biosynthesis
                    • Autoimmune Diseases
                    • B-Lymphocytes / immunology
                    • B-Lymphocytes / metabolism
                    • B-Lymphocytes / pathology
                    • Blood-Retinal Barrier
                    • Case-Control Studies
                    • Cell Movement
                    • Chromatography, Liquid
                    • Gene Expression Regulation
                    • Granulocytes / immunology
                    • Granulocytes / metabolism
                    • Granulocytes / pathology
                    • Horse Diseases / genetics
                    • Horse Diseases / immunology
                    • Horse Diseases / metabolism
                    • Horse Diseases / pathology
                    • Horses
                    • Immunoprecipitation
                    • Mass Spectrometry
                    • Molecular Sequence Annotation
                    • Protein Binding
                    • T-Lymphocytes / immunology
                    • T-Lymphocytes / metabolism
                    • T-Lymphocytes / pathology
                    • Talin / genetics
                    • Talin / immunology
                    • Talin / metabolism
                    • Thy-1 Antigens / genetics
                    • Thy-1 Antigens / immunology
                    • Thy-1 Antigens / metabolism
                    • Uvea / immunology
                    • Uvea / metabolism
                    • Uvea / pathology
                    • Uveitis / immunology
                    • Uveitis / metabolism
                    • Uveitis / pathology
                    • Uveitis / veterinary

                    Citations

                    This article has been cited 9 times.
                    1. Degroote RL, Schmalen A, Hauck SM, Deeg CA. Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis. Biomedicines 2023 Dec 20;12(1).
                      doi: 10.3390/biomedicines12010019pubmed: 38275380google scholar: lookup
                    2. Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro. Int J Mol Sci 2022 Aug 23;23(17).
                      doi: 10.3390/ijms23179555pubmed: 36076947google scholar: lookup
                    3. Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
                      doi: 10.3389/fimmu.2020.609855pubmed: 33488614google scholar: lookup
                    4. 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.
                      doi: 10.3389/fimmu.2019.03064pubmed: 32010136google scholar: lookup
                    5. Schauer M, Kleinwort KJH, Degroote RL, Wiedemann C, Kremmer E, Hauck SM, Deeg CA. Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity. Sci Rep 2018 Aug 17;8(1):12332.
                      doi: 10.1038/s41598-018-30753-7pubmed: 30120291google scholar: lookup
                    6. Pepple KL, Rotkis L, Wilson L, Sandt A, Van Gelder RN. Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats. Invest Ophthalmol Vis Sci 2015 Dec;56(13):8449-56.
                      doi: 10.1167/iovs.15-17524pubmed: 26747776google scholar: lookup
                    7. Uhl PB, Amann B, Hauck SM, Deeg CA. Novel localization of peripherin 2, the photoreceptor-specific retinal degeneration slow protein, in retinal pigment epithelium. Int J Mol Sci 2015 Jan 26;16(2):2678-92.
                      doi: 10.3390/ijms16022678pubmed: 25629227google scholar: lookup
                    8. Maan ZN, Rennert RC, Koob TJ, Januszyk M, Li WW, Gurtner GC. Cell recruitment by amnion chorion grafts promotes neovascularization. J Surg Res 2015 Feb;193(2):953-962.
                      doi: 10.1016/j.jss.2014.08.045pubmed: 25266600google scholar: lookup
                    9. Degroote RL, Hauck SM, Amann B, Hirmer S, Ueffing M, Deeg CA. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis. PLoS One 2014;9(3):e91684.
                      doi: 10.1371/journal.pone.0091684pubmed: 24614191google scholar: lookup