Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with multiple sclerosis
Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with multiple sclerosis
Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterized. Here we focussed on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular overabundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.
Multiple Sclerosis, CD161, proteomics, T cells, neutrophils
Smith, Katie J.
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Lim, Zachary
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Vermeren, Sonja
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Miron, Veronique E.
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Dimeloe, Sarah
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Davidson, Donald J.
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Williams, Anna
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Gwyer Findlay, Emily
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30 May 2025
Smith, Katie J.
55a94661-6f88-4f6a-9e2e-f9cc4ba9988e
Lim, Zachary
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Vermeren, Sonja
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Miron, Veronique E.
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Dimeloe, Sarah
b153e5e9-5af8-406c-a0a8-bc924a168a5b
Davidson, Donald J.
9712de87-f4c2-4a82-9d02-3b16a3bd5743
Williams, Anna
73534048-67ca-4066-a0f0-5e6bed1ceaca
Gwyer Findlay, Emily
b6787bbb-66ad-435c-ad2c-c18ffaf6b7d8
Smith, Katie J., Lim, Zachary, Vermeren, Sonja, Miron, Veronique E., Dimeloe, Sarah, Davidson, Donald J., Williams, Anna and Gwyer Findlay, Emily
(2025)
Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with multiple sclerosis.
Clinical & Experimental Immunology, 219 (1), [uxae115].
(doi:10.1093/cei/uxae115).
Abstract
Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterized. Here we focussed on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular overabundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.
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Accepted/In Press date: 19 December 2024
e-pub ahead of print date: 16 January 2025
Published date: 30 May 2025
Keywords:
Multiple Sclerosis, CD161, proteomics, T cells, neutrophils
Identifiers
Local EPrints ID: 496899
URI: http://eprints.soton.ac.uk/id/eprint/496899
ISSN: 0009-9104
PURE UUID: 8ae7fd3a-a272-4c8d-8251-9d7b323c0f57
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Date deposited: 08 Jan 2025 12:37
Last modified: 31 Jan 2026 07:42
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Contributors
Author:
Katie J. Smith
Author:
Zachary Lim
Author:
Sonja Vermeren
Author:
Veronique E. Miron
Author:
Sarah Dimeloe
Author:
Donald J. Davidson
Author:
Anna Williams
Author:
Emily Gwyer Findlay
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