A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In MS, CNS-infiltrating monocytes differentiate to tissue resident macrophages which are found in large numbers within the injured areas of the brain where they play a central role in driving disease progr...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1628398/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849412229750849536 |
|---|---|
| author | Marina Rode von Essen Marie Mathilde Hansen Sahla El Mahdaoui Victoria Hyslop Hvalkof Malene Bredahl Hansen Sophie Buhelt Finn Sellebjerg Finn Sellebjerg |
| author_facet | Marina Rode von Essen Marie Mathilde Hansen Sahla El Mahdaoui Victoria Hyslop Hvalkof Malene Bredahl Hansen Sophie Buhelt Finn Sellebjerg Finn Sellebjerg |
| author_sort | Marina Rode von Essen |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In MS, CNS-infiltrating monocytes differentiate to tissue resident macrophages which are found in large numbers within the injured areas of the brain where they play a central role in driving disease progression through demyelination and tissue destruction. However, infiltrating monocytes and their derivative macrophages can also serve protective functions. In this study we investigated a possible role of intrathecal mononuclear phagocytes (infiltrating monocytes and macrophages) expressing dual immunoglobulin domain-containing cell adhesion molecule (DICAM) in neuroinflammation. Compared to symptomatic controls (n = 14), treatment-naïve patients with relapsing-remitting MS (n = 21) had a reduced prevalence of DICAM+ mononuclear phagocytes in CSF. When patients were treated with natalizumab (n = 12), an antibody blocking migration of blood leukocytes to the CNS, we observed that DICAM+ monocytes were still recruited to the CSF and that the level of soluble DICAM (sDICAM) in CSF was significantly increased in natalizumab-treated patients (n = 42) compared to untreated patients (n = 43). sDICAM and the prevalence of DICAM+ mononuclear phagocytes in CSF furthermore correlated negatively with concentrations of various cytokines, including TNFα. Analysing the functional properties of DICAM showed that LPS-induced TNFα-production in mononuclear phagocytes was effectively reduced by signalling through surface-bound DICAM. This discovery, together with the observation of a high prevalence of infiltrating DICAM+ mononuclear phagocytes in individuals with no disease or in which disease was kept under control, suggests an immunomodulatory role of DICAM+ mononuclear phagocytes. DICAM has been shown to engage in homophilic interactions with DICAM expressed on the same cell. If sDICAM in a similar way can engage with DICAM on adjacent cells, the increased intrathecal sDICAM of natalizumab-treated patients may help regulate inflammation in a paracrine way. Overall, our data suggest that DICAM+ mononuclear phagocytes play a role in controlling neuroinflammation. |
| format | Article |
| id | doaj-art-ff09aacd95d64333b27b0191ac5d0091 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ff09aacd95d64333b27b0191ac5d00912025-08-20T03:34:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16283981628398A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosisMarina Rode von Essen0Marie Mathilde Hansen1Sahla El Mahdaoui2Victoria Hyslop Hvalkof3Malene Bredahl Hansen4Sophie Buhelt5Finn Sellebjerg6Finn Sellebjerg7Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In MS, CNS-infiltrating monocytes differentiate to tissue resident macrophages which are found in large numbers within the injured areas of the brain where they play a central role in driving disease progression through demyelination and tissue destruction. However, infiltrating monocytes and their derivative macrophages can also serve protective functions. In this study we investigated a possible role of intrathecal mononuclear phagocytes (infiltrating monocytes and macrophages) expressing dual immunoglobulin domain-containing cell adhesion molecule (DICAM) in neuroinflammation. Compared to symptomatic controls (n = 14), treatment-naïve patients with relapsing-remitting MS (n = 21) had a reduced prevalence of DICAM+ mononuclear phagocytes in CSF. When patients were treated with natalizumab (n = 12), an antibody blocking migration of blood leukocytes to the CNS, we observed that DICAM+ monocytes were still recruited to the CSF and that the level of soluble DICAM (sDICAM) in CSF was significantly increased in natalizumab-treated patients (n = 42) compared to untreated patients (n = 43). sDICAM and the prevalence of DICAM+ mononuclear phagocytes in CSF furthermore correlated negatively with concentrations of various cytokines, including TNFα. Analysing the functional properties of DICAM showed that LPS-induced TNFα-production in mononuclear phagocytes was effectively reduced by signalling through surface-bound DICAM. This discovery, together with the observation of a high prevalence of infiltrating DICAM+ mononuclear phagocytes in individuals with no disease or in which disease was kept under control, suggests an immunomodulatory role of DICAM+ mononuclear phagocytes. DICAM has been shown to engage in homophilic interactions with DICAM expressed on the same cell. If sDICAM in a similar way can engage with DICAM on adjacent cells, the increased intrathecal sDICAM of natalizumab-treated patients may help regulate inflammation in a paracrine way. Overall, our data suggest that DICAM+ mononuclear phagocytes play a role in controlling neuroinflammation.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1628398/fullDICAMneuroinflammationmononuclear phagocytesmonocytesmacrophagesmultiple sclerosis |
| spellingShingle | Marina Rode von Essen Marie Mathilde Hansen Sahla El Mahdaoui Victoria Hyslop Hvalkof Malene Bredahl Hansen Sophie Buhelt Finn Sellebjerg Finn Sellebjerg A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis Frontiers in Immunology DICAM neuroinflammation mononuclear phagocytes monocytes macrophages multiple sclerosis |
| title | A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis |
| title_full | A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis |
| title_fullStr | A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis |
| title_full_unstemmed | A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis |
| title_short | A role for DICAM+ mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis |
| title_sort | role for dicam mononuclear phagocytes in controlling neuroinflammation in multiple sclerosis |
| topic | DICAM neuroinflammation mononuclear phagocytes monocytes macrophages multiple sclerosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1628398/full |
| work_keys_str_mv | AT marinarodevonessen arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT mariemathildehansen arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT sahlaelmahdaoui arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT victoriahyslophvalkof arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT malenebredahlhansen arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT sophiebuhelt arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT finnsellebjerg arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT finnsellebjerg arolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT marinarodevonessen rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT mariemathildehansen rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT sahlaelmahdaoui rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT victoriahyslophvalkof rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT malenebredahlhansen rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT sophiebuhelt rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT finnsellebjerg rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis AT finnsellebjerg rolefordicammononuclearphagocytesincontrollingneuroinflammationinmultiplesclerosis |