Unveiling differential responses of granulocytes to distinct immunostimulants with implications in autoimmune uveitis.
Biomedicines 12:19 (2023)
The perception of circulating granulocytes as cells with a predetermined immune response mainly triggered by pathogens is evolving, recognizing their functional heterogeneity and adaptability, particularly within the neutrophil subset. The involvement of these cells in the pathophysiology of autoimmune uveitis has become increasingly clear, yet their exact role remains elusive. We used an equine model for autoimmune-mediated recurrent pan-uveitis to investigate early responses of granulocytes in different inflammatory environments. For this purpose, we performed differential proteomics on granulocytes from healthy and diseased horses stimulated with IL8, LPS, or PMA. Compared to healthy horses, granulocytes from the recurrent uveitis model significantly changed the cellular abundance of 384 proteins, with a considerable number of specific changes for each stimulant. To gain more insight into the functional impact of these stimulant-specific proteome changes in ERU pathogenesis, we used Ingenuity Pathway Analysis for pathway enrichment. This resulted in specific reaction patterns for each stimulant, with IL8 predominantly promoting Class I MHC-mediated antigen processing and presentation, LPS enhancing processes in phospholipid biosynthesis, and PMA, clearly inducing neutrophil degranulation. These findings shed light on the remarkably differentiated responses of neutrophils, offering valuable insights into their functional heterogeneity in a T-cell-driven disease. Raw data are available via ProteomeXchange with identifier PXD013648.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Eru ; Il8 ; Lps ; Pma ; Pmn ; Differential Proteomics ; Granulocyte ; Granulocyte Heterogeneity ; Innate Immune Cell Activation ; Pathway Analysis
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Language
english
Publication Year
2023
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0
HGF-reported in Year
2023
ISSN (print) / ISBN
2227-9059
e-ISSN
2227-9059
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Volume: 12,
Issue: 1,
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Article Number: 19
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MDPI
Publishing Place
Basel, Switzerland
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-505700-001
A-630700-001
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Erfassungsdatum
2024-01-31