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Proteomics2017; 17(19); doi: 10.1002/pmic.201700013

Proteome Dynamics in Biobanked Horse Peripheral Blood Derived Lymphocytes (PBL) with Induced Autoimmune Uveitis.

Abstract: Equine recurrent uveitis is the only spontaneous model for recurrent autoimmune uveitis in humans, where T cells target retinal proteins. Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with interphotoreceptor retinoid binding protein induced uveitis sampled before (Day 0), during (Day 15), and after uveitic attack (Day 23). Relative protein abundances of PBL were investigated in a quantitative, label-free differential proteome analysis in cells that were kept frozen for 14 years since the initial experiment. Quantitative data could be acquired for 2632 proteins at all three time points. Profound changes (≥2-fold change) in PBL protein abundance were observed when comparing Day 0 with 15, representing acute inflammation (1070 regulated proteins) and Day 0 with 23 (cessation; 1571 regulated). Significant differences applied to proteins with functions in integrin signaling during active uveitis, involving "Erk and pi-3 kinase are necessary for collagen binding in corneal epithelia," "integrins in angiogenesis," and "integrin-linked kinase signaling" pathways. In contrast, at cessation of uveitic attack, significantly changed proteins belonged to pathways of "nongenotropic androgen signaling," "classical complement pathway," and "Amb2 integrin signaling." Several members of respective pathways were earlier shown to be changed in naturally occurring uveitis, underscoring the significance of these findings here and proofing the value of the induced model in mimicking spontaneous autoimmune uveitis. All MS data have been deposited to the ProteomeXchange consortium via the PRIDE partner repository (dataset identifier PXD005580).
Publication Date: 2017-08-29 PubMed ID: 28846213DOI: 10.1002/pmic.201700013Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper is a deep investigation into the differences in peripheral blood derived lymphocytes (PBL) proteomes during normal conditions and autoaggressive states, in the context of Equine recurrent uveitis, which serves as a model for human autoimmune recurrent uveitis.

Objective of the Research

  • The research aimed to understand the dynamics of proteomes in PBL during autoimmune uveitis, a prevalent ocular autoimmune disorder that leads to inflammation and could potentially result in blindness. This disorder has been frequently encountered in humans and horses.

Research Methodology

  • The researchers utilized samples from a specific case of equine recurrent uveitis, which were collected at different stages: pre-attack (Day 0), during attack (Day 15), and post-attack (Day 23).
  • These samples, frozen for 14 years since their collection, were studied using a quantitative, differentiating proteome analysis to observe how the protein abundances in the PBL fluctuated.

Key Findings

  • Through their research, the team was able to acquire quantitative data on 2632 proteins across all the three time points.
  • There were profound changes in the PBL protein abundance when Day 0 (pre-attack) was compared with Day 15 (during attack) with 1070 regulated proteins, and Day 0 with Day 23 (post-attack) with 1571 regulated proteins.
  • Significant differences were observed in proteins with roles in integrin signaling during active uveitis, with changes noted in pathways, including those relating to collagen binding in corneal epithelia, integrins in angiogenesis, and integrin-linked kinase signaling.
  • At the cessation of uveitic attack, different proteins, belonging to the pathways of non-genotropic androgen signaling, classical complement pathway, and Amb2 integrin signaling displayed significant changes.

Significance of the Research

  • This investigation provides valuable data on the dynamics of PBL proteomes during autoimmune uveitis.
  • The findings confirm other research indicating changes in these pathways in naturally occurring uveitis, which bolsters the reliability of the induced model for studying the spontaneous version of the disorder.

Finally, all mass spectrometry data generated during the research has been deposited for public view in the ProteomeXchange consortium via the PRIDE repository.

Cite This Article

APA
Hauck SM, Lepper MF, Hertl M, Sekundo W, Deeg CA. (2017). Proteome Dynamics in Biobanked Horse Peripheral Blood Derived Lymphocytes (PBL) with Induced Autoimmune Uveitis. Proteomics, 17(19). https://doi.org/10.1002/pmic.201700013

Publication

ISSN: 1615-9861
NlmUniqueID: 101092707
Country: Germany
Language: English
Volume: 17
Issue: 19

Researcher Affiliations

Hauck, Stefanie M
  • Research Unit Protein Science, Helmholtz Center Munich, Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Lepper, Marlen F
  • Research Unit Protein Science, Helmholtz Center Munich, Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Hertl, Michael
  • Department of Allergy and Dermatology, Philipps University of Marburg, Marburg, Germany.
Sekundo, Walter
  • Department of Ophthalmology, Philipps University of Marburg, Marburg, Germany.
Deeg, Cornelia A
  • Experimental Ophthalmology, Philipps University of Marburg, Marburg, Germany.
  • Chair for Animal Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.

MeSH Terms

  • Animals
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / veterinary
  • Biological Specimen Banks
  • Cells, Cultured
  • Horse Diseases / immunology
  • Horse Diseases / metabolism
  • Horses
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Proteome / analysis
  • Retina / cytology
  • Retina / immunology
  • Retina / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Uveitis / metabolism
  • Uveitis / veterinary

Citations

This article has been cited 8 times.
  1. 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
  2. Kleinwort KJH, Hobmaier BF, Mayer R, Hölzel C, Degroote RL, Märtlbauer E, Hauck SM, Deeg CA. Mycobacterium avium subsp. paratuberculosis Proteome Changes Profoundly in Milk. Metabolites 2021 Aug 20;11(8).
    doi: 10.3390/metabo11080549pubmed: 34436489google scholar: lookup
  3. 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.
    doi: 10.3389/fimmu.2021.601619pubmed: 34385998google scholar: lookup
  4. Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
    doi: 10.3389/fimmu.2020.609855pubmed: 33488614google scholar: lookup
  5. 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
  6. Kleinwort KJH, Hauck SM, Degroote RL, Scholz AM, Hölzel C, Maertlbauer EP, Deeg C. Peripheral blood bovine lymphocytes and MAP show distinctly different proteome changes and immune pathways in host-pathogen interaction. PeerJ 2019;7:e8130.
    doi: 10.7717/peerj.8130pubmed: 31788366google scholar: lookup
  7. 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.
    doi: 10.1111/vop.12704pubmed: 31441218google scholar: lookup
  8. 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