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Home / Equine Research Bank / Int J Mol Sci / Pre-Activated Granulocytes from an Autoimmune Uveitis Model ...
International journal of molecular sciences2022; 23(17); doi: 10.3390/ijms23179555

Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro.

Abstract: In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways "PKA signaling", "PTEN signaling" and "leukocyte extravasation". Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.
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Publication Date: 2022-08-23 PubMed ID: 36076947PubMed Central: PMC9455241DOI: 10.3390/ijms23179555Google Scholar: Lookup
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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 study investigates the role of granulocytes in autoimmune uveitis, particularly equine recurrent uveitis (ERU), by analyzing their response to IL8 stimulation. Findings suggest significant differences in protein abundance, with MMP25 identified as a potential regulator of granulocyte activity, which could guide new approaches in diagnosing and treating uveitis.

Investigating Granulocytes in Autoimmune Uveitis

  • The researchers studied the involvement of granulocytes in the development of autoimmune-mediated uveitis, a condition characterized by inflammation of the eye tissues.
  • The focus was on equine recurrent uveitis (ERU), a type of uveitis that occurs in horses and can provide insights into the human variant of the disease.
  • Granulocytes, a type of immune cell, were found to be pre-activated in ERU, suggesting they may contribute to the development and progression of the disease.

Examining Granulocytes Response to IL8 Stimulation

  • The researchers introduced IL8, a pro-inflammatory molecule, to granulocytes from healthy and ERU horses to study the cellular response.
  • They used differential proteomics, a technique that examines the differences in protein levels between cells, to analyze the effects of the stimulation.
  • The proteomic analysis revealed a significant difference in the protein abundance of 170 proteins in ERU granulocytes after IL8 stimulation.

Identifying Activated Pathways

  • Further analysis identified three activated canonical pathways in the ERU granulocytes upon IL8 stimulation: PKA signaling, PTEN signaling and leukocyte extravasation.
  • Leukocyte extravasation, a process where leukocytes (white blood cells) move out from the blood circulation into tissues, was of particular interest.
  • The researchers discovered that a membrane-type GPI-anchored protease called MMP25, associated with the leukocyte extravasation pathway, was increased in IL8-stimulated ERU granulocytes.

Possible Implications for Uveitis Diagnostics and Therapy

  • The findings suggest that MMP25 may regulate granulocyte extravasation in uveitis, which contributes to the impaired integrity of the blood-retina-barrier, a crucial element in the pathology of uveitis.
  • The researchers therefore propose that MMP25 could serve as a target in developing new approaches for diagnosing and treating non-infectious ocular diseases like uveitis.

Cite This Article

APA
Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. (2022). Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro. Int J Mol Sci, 23(17). https://doi.org/10.3390/ijms23179555

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 23
Issue: 17

Researcher Affiliations

Hoffmann, Anne L C
  • Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.
Hauck, Stefanie M
  • Research Unit Protein Science, 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.
Degroote, Roxane L
  • Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.

MeSH Terms

  • Animals
  • Autoimmune Diseases
  • Granulocytes / metabolism
  • Horse Diseases / metabolism
  • Horses
  • Interleukin-8
  • Proteomics
  • Recurrence
  • Uveitis / metabolism

Grant Funding

  • DE 719/4-3 / Deutsche Forschungsgemeinschaft

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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