Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation
Abstract Background Multiple sclerosis (MS) involves a misdirected immune attack against myelin in the brain and spinal cord, leading to profound neuroinflammation and neurodegeneration. While the mechanisms of disease pathogenesis have been widely studied, the suppression mechanisms that lead to th...
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-019-1522-4 |
| _version_ | 1819265496320573440 |
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| author | Juan M. Ilarregui Gijs Kooij Ernesto Rodríguez Susanne M. A. van der Pol Nathalie Koning Hakan Kalay Joost C. van der Horst Sandra J. van Vliet Juan J. García-Vallejo Helga E. de Vries Yvette van Kooyk |
| author_facet | Juan M. Ilarregui Gijs Kooij Ernesto Rodríguez Susanne M. A. van der Pol Nathalie Koning Hakan Kalay Joost C. van der Horst Sandra J. van Vliet Juan J. García-Vallejo Helga E. de Vries Yvette van Kooyk |
| author_sort | Juan M. Ilarregui |
| collection | DOAJ |
| description | Abstract Background Multiple sclerosis (MS) involves a misdirected immune attack against myelin in the brain and spinal cord, leading to profound neuroinflammation and neurodegeneration. While the mechanisms of disease pathogenesis have been widely studied, the suppression mechanisms that lead to the resolution of the autoimmune response are still poorly understood. Here, we investigated the role of the C-type lectin receptor macrophage galactose-type lectin (MGL), usually expressed on tolerogenic antigen-presenting cells (APCs), as a negative regulator of autoimmune-driven neuroinflammation. Methods We used in silico, immunohistochemical, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry analysis to explore the expression and functionality of MGL in human macrophages and microglia, as well as in MS post-mortem tissue. In vitro, we studied the capacity of MGL to mediate apoptosis of experimental autoimmune encephalomyelitis (EAE)-derived T cells and mouse CD4+ T cells. Finally, we evaluated in vivo and ex vivo the immunomodulatory potential of MGL in EAE. Results MGL plays a critical role in the resolution phase of EAE as MGL1-deficient (Clec10a −/−) mice showed a similar day of onset but experienced a higher clinical score to that of WT littermates. We demonstrate that the mouse ortholog MGL1 induces apoptosis of autoreactive T cells and diminishes the expression of pro-inflammatory cytokines and inflammatory autoantibodies. Moreover, we show that MGL1 but not MGL2 induces apoptosis of activated mouse CD4+ T cells in vitro. In human settings, we show that MGL expression is increased in active MS lesions and on alternatively activated microglia and macrophages which, in turn, induces the secretion of the immunoregulatory cytokine IL-10, underscoring the clinical relevance of this lectin. Conclusions Our results show a new role of MGL-expressing APCs as an anti-inflammatory mechanism in autoimmune neuroinflammation by dampening pathogenic T and B cell responses, uncovering a novel clue for neuroprotective therapeutic strategies with relevance for in MS clinical applications. |
| first_indexed | 2024-12-23T20:46:18Z |
| format | Article |
| id | doaj.art-22f87aeffcb24a268513be628fe3e17d |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-23T20:46:18Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-22f87aeffcb24a268513be628fe3e17d2022-12-21T17:31:46ZengBMCJournal of Neuroinflammation1742-20942019-06-0116111410.1186/s12974-019-1522-4Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammationJuan M. Ilarregui0Gijs Kooij1Ernesto Rodríguez2Susanne M. A. van der Pol3Nathalie Koning4Hakan Kalay5Joost C. van der Horst6Sandra J. van Vliet7Juan J. García-Vallejo8Helga E. de Vries9Yvette van Kooyk10Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, VUmc MS Center, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, VUmc MS Center, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, VUmc MS Center, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit AmsterdamAbstract Background Multiple sclerosis (MS) involves a misdirected immune attack against myelin in the brain and spinal cord, leading to profound neuroinflammation and neurodegeneration. While the mechanisms of disease pathogenesis have been widely studied, the suppression mechanisms that lead to the resolution of the autoimmune response are still poorly understood. Here, we investigated the role of the C-type lectin receptor macrophage galactose-type lectin (MGL), usually expressed on tolerogenic antigen-presenting cells (APCs), as a negative regulator of autoimmune-driven neuroinflammation. Methods We used in silico, immunohistochemical, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry analysis to explore the expression and functionality of MGL in human macrophages and microglia, as well as in MS post-mortem tissue. In vitro, we studied the capacity of MGL to mediate apoptosis of experimental autoimmune encephalomyelitis (EAE)-derived T cells and mouse CD4+ T cells. Finally, we evaluated in vivo and ex vivo the immunomodulatory potential of MGL in EAE. Results MGL plays a critical role in the resolution phase of EAE as MGL1-deficient (Clec10a −/−) mice showed a similar day of onset but experienced a higher clinical score to that of WT littermates. We demonstrate that the mouse ortholog MGL1 induces apoptosis of autoreactive T cells and diminishes the expression of pro-inflammatory cytokines and inflammatory autoantibodies. Moreover, we show that MGL1 but not MGL2 induces apoptosis of activated mouse CD4+ T cells in vitro. In human settings, we show that MGL expression is increased in active MS lesions and on alternatively activated microglia and macrophages which, in turn, induces the secretion of the immunoregulatory cytokine IL-10, underscoring the clinical relevance of this lectin. Conclusions Our results show a new role of MGL-expressing APCs as an anti-inflammatory mechanism in autoimmune neuroinflammation by dampening pathogenic T and B cell responses, uncovering a novel clue for neuroprotective therapeutic strategies with relevance for in MS clinical applications.http://link.springer.com/article/10.1186/s12974-019-1522-4C-type lectin receptorsMGLMultiple sclerosisExperimental autoimmune encephalomyelitisMicrogliaInflammation |
| spellingShingle | Juan M. Ilarregui Gijs Kooij Ernesto Rodríguez Susanne M. A. van der Pol Nathalie Koning Hakan Kalay Joost C. van der Horst Sandra J. van Vliet Juan J. García-Vallejo Helga E. de Vries Yvette van Kooyk Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation Journal of Neuroinflammation C-type lectin receptors MGL Multiple sclerosis Experimental autoimmune encephalomyelitis Microglia Inflammation |
| title | Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation |
| title_full | Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation |
| title_fullStr | Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation |
| title_full_unstemmed | Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation |
| title_short | Macrophage galactose-type lectin (MGL) is induced on M2 microglia and participates in the resolution phase of autoimmune neuroinflammation |
| title_sort | macrophage galactose type lectin mgl is induced on m2 microglia and participates in the resolution phase of autoimmune neuroinflammation |
| topic | C-type lectin receptors MGL Multiple sclerosis Experimental autoimmune encephalomyelitis Microglia Inflammation |
| url | http://link.springer.com/article/10.1186/s12974-019-1522-4 |
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