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Home / Equine Research Bank / Biomedicines / Unveiling Differential Responses of Granulocytes to Distinct...
Biomedicines2023; 12(1); 19; doi: 10.3390/biomedicines12010019

Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis.

Abstract: 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 Date: 2023-12-20 PubMed ID: 38275380PubMed Central: PMC10812922DOI: 10.3390/biomedicines12010019Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates how granulocytes, a type of immune cell, respond to different stimuli in an autoimmune disease called recurrent uveitis, using an equine model. By using differential proteomics, researchers found that granulocytes responded differently to different types of immune stimulants and that their responses were altered in horses with recurrent uveitis.

Study Background and Objective

  • The study is centered on granulocytes, primarily a subset called neutrophils. Traditionally viewed as cells with predetermined immune responses primarily triggered by pathogens, recent research recognises the functional diversity and adaptability of granulocytes.
  • The researchers aim to clarify the role of granulocytes in autoimmune uveitis, a repetitive inflammatory eye disease. While it is known that these cells participate in the condition’s pathophysiology, their exact contribution remains unknown.

Method and Experiment

  • An equine model for autoimmune-mediated recurrent pan-uveitis, an advanced form of uveitis, was employed. The researchers investigated the preliminary responses of granulocytes under different inflammatory environments to comprehend their adaptability and variations in reactions.
  • Granulocytes from both healthy and diseased horses were isolated and stimulated with three immunostimulants – IL8, LPS, and PMA. Subsequently, researchers carried out differential proteomics, a technique comparing protein profiles, to highlight the alterations in reaction based on the health status of the host and the type of stimulant.

Results and Findings

  • The granulocytes from diseased horses exhibited significant changes in the cellular abundance of 384 proteins, compared to those from healthy horses. These changes were primarily unique to each stimulant used.
  • Further examination of these alterations using “Ingenuity Pathway Analysis” for pathway enrichment resulted in distinct reaction patterns for each stimulant. IL8 was found to encourage Class I MHC-mediated antigen processing and presentation most. LPS enhanced processes related to phospholipid biosynthesis, while PMA was seen to trigger neutrophil degranulation conclusively.

Research Implications

  • The study discloses vital information regarding the distinctive responses of neutrophils, demonstrating their functional heterogeneity during a T-cell-driven disease.
  • These findings assist in furthering our understanding about the specific roles of granulocytes during autoimmune responses, thereby providing potential pathways for developing targeted therapies for such conditions.

Cite This Article

APA
Degroote RL, Schmalen A, Hauck SM, Deeg CA. (2023). Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis. Biomedicines, 12(1), 19. https://doi.org/10.3390/biomedicines12010019

Publication

Biomedicines
ISSN: 2227-9059
NlmUniqueID: 101691304
Country: Switzerland
Language: English
Volume: 12
Issue: 1
PII: 19

Researcher Affiliations

Degroote, Roxane L
  • Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.
Schmalen, Adrian
  • Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.
  • Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health, D-80939 Munich, Germany.
Hauck, Stefanie M
  • Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health, D-80939 Munich, Germany.
Deeg, Cornelia A
  • Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.

Grant Funding

  • DFG DE 719/4-3 / Deutsche Forschungsgemeinschaft

Conflict of Interest Statement

The authors declare no conflict of interest.

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