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Degroote, R.L.* ; Schmalen, A. ; Hauck, S.M. ; Deeg, C.A.*

Unveiling differential responses of granulocytes to distinct immunostimulants with implications in autoimmune uveitis.

Biomedicines 12:19 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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

Corresponding Author

Keywords Eru ; Il8 ; Lps ; Pma ; Pmn ; Differential Proteomics ; Granulocyte ; Granulocyte Heterogeneity ; Innate Immune Cell Activation ; Pathway Analysis

ISSN (print) / ISBN 2227-9059

e-ISSN 2227-9059

Journal Biomedicines

Quellenangaben Volume: 12, Issue: 1, Article Number: 19

Publisher MDPI

Publishing Place Basel, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)