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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.<\/jats:p>","DOI":"10.1093\/cei\/uxae115","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T07:27:25Z","timestamp":1733729245000},"source":"Crossref","is-referenced-by-count":4,"title":["Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis"],"prefix":"10.1093","volume":"219","author":[{"given":"Katie J","family":"Smith","sequence":"first","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Southampton , Southampton ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Vermeren","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique E","family":"Miron","sequence":"additional","affiliation":[{"name":"United Kingdom Dementia Research Institute at The University of Edinburgh , Edinburgh ,","place":["UK"]},{"name":"Keenan Research Centre for Biomedical Sciences at St. Michael\u2019s Hospital, Unity Health Toronto , Toronto, ON ,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dimeloe","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, University of Birmingham , Birmingham ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J","family":"Davidson","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6329-382X","authenticated-orcid":false,"given":"Anna","family":"Williams","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute of Regeneration and Repair, University of Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-6589","authenticated-orcid":false,"given":"Emily","family":"Gwyer Findlay","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh ,","place":["UK"]},{"name":"School of Biological 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