CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder
Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoantibody-triggered central nervous system (CNS) demyelinating disease that primarily affects the spinal cord, optic nerves and brainstem. Among the first responders to CNS injury, microglia are prominent players that drive...
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BMC
2024-11-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-024-03305-2 |
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| author | Wenjun Zhang Yali Han Huachen Huang Yue Su Honglei Ren Caiyun Qi Jinyi Li Huaijin Yang Jing Xu Guoqiang Chang Wenjin Qiu Qiang Liu Ting Chang |
| author_facet | Wenjun Zhang Yali Han Huachen Huang Yue Su Honglei Ren Caiyun Qi Jinyi Li Huaijin Yang Jing Xu Guoqiang Chang Wenjin Qiu Qiang Liu Ting Chang |
| author_sort | Wenjun Zhang |
| collection | DOAJ |
| description | Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoantibody-triggered central nervous system (CNS) demyelinating disease that primarily affects the spinal cord, optic nerves and brainstem. Among the first responders to CNS injury, microglia are prominent players that drive NMOSD lesion formation. However, the key molecular switches controlling the detrimental activity of microglia in NMOSD are poorly understood. CD22 governs the activity of innate and adaptive immunity. In this study, we investigated to what extent and by what mechanisms CD22 may modulate microglial activity, neuroinflammation and CNS lesion formation. Methods To determine the expression profile of CD22 in NMOSD, we performed single-cell sequencing and flow cytometry analysis of immune cells from human peripheral blood. We investigated the potential effects and mechanisms of CD22 blockade on microglial activity, leukocyte infiltration and CNS demyelination in a mouse model of NMOSD induced by injection of NMOSD patient serum-derived AQP4-IgG and human complement. Results Single-cell sequencing and flow cytometry analysis revealed that CD22 was expressed in B cells, neutrophils, monocytes and microglia-derived exosomes in human peripheral blood from NMOSD patients and controls (n = 5 per group). In a mouse model of NMOSD, CD22 was expressed in B cells, neutrophils, monocytes and microglia (n = 8 per group). In NMOSD mice, CD22 blockade significantly increased the number of CNS lesions, astrocyte loss and demyelination, accompanied by increased inflammatory activity and phagocytosis in microglia. Furthermore, the detrimental effects of CD22 blockade were significantly alleviated in NMOSD mice subjected to depletion of microglia or Gr-1+ myeloid cells, suggesting the involvement of microglia and peripheral Gr-1+ myeloid cells. Additionally, CD22 blockade also led to significantly reduced phosphorylation of SYK and GSK3β in NMOSD. Notably, the detrimental effects of CD22 blockade were greatly diminished in NMOSD mice receiving the phosphorylated SYK inhibitor R406. Conclusions Our findings revealed a previously unrecognized role of CD22 as a key molecular switch that governs the detrimental effects of microglia and Gr-1+ myeloid cells in NMOSD, which paves the way for the future design of immune therapies for NMOSD. Graphical abstract |
| format | Article |
| id | doaj-art-0d287cb06a6b470a9a12620f8299f9cc |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Journal of Neuroinflammation |
| spelling | doaj-art-0d287cb06a6b470a9a12620f8299f9cc2024-12-01T12:37:49ZengBMCJournal of Neuroinflammation1742-20942024-11-0121111710.1186/s12974-024-03305-2CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorderWenjun Zhang0Yali Han1Huachen Huang2Yue Su3Honglei Ren4Caiyun Qi5Jinyi Li6Huaijin Yang7Jing Xu8Guoqiang Chang9Wenjin Qiu10Qiang Liu11Ting Chang12Tianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalDepartment of Neurology, Tangdu Hospital, Air Force Medical UniversityTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityTianjin Neurological Institute, Department of Neurology, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Ministry of Education, Tianjin Medical University General HospitalDepartment of Neurology, Tangdu Hospital, Air Force Medical UniversityAbstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoantibody-triggered central nervous system (CNS) demyelinating disease that primarily affects the spinal cord, optic nerves and brainstem. Among the first responders to CNS injury, microglia are prominent players that drive NMOSD lesion formation. However, the key molecular switches controlling the detrimental activity of microglia in NMOSD are poorly understood. CD22 governs the activity of innate and adaptive immunity. In this study, we investigated to what extent and by what mechanisms CD22 may modulate microglial activity, neuroinflammation and CNS lesion formation. Methods To determine the expression profile of CD22 in NMOSD, we performed single-cell sequencing and flow cytometry analysis of immune cells from human peripheral blood. We investigated the potential effects and mechanisms of CD22 blockade on microglial activity, leukocyte infiltration and CNS demyelination in a mouse model of NMOSD induced by injection of NMOSD patient serum-derived AQP4-IgG and human complement. Results Single-cell sequencing and flow cytometry analysis revealed that CD22 was expressed in B cells, neutrophils, monocytes and microglia-derived exosomes in human peripheral blood from NMOSD patients and controls (n = 5 per group). In a mouse model of NMOSD, CD22 was expressed in B cells, neutrophils, monocytes and microglia (n = 8 per group). In NMOSD mice, CD22 blockade significantly increased the number of CNS lesions, astrocyte loss and demyelination, accompanied by increased inflammatory activity and phagocytosis in microglia. Furthermore, the detrimental effects of CD22 blockade were significantly alleviated in NMOSD mice subjected to depletion of microglia or Gr-1+ myeloid cells, suggesting the involvement of microglia and peripheral Gr-1+ myeloid cells. Additionally, CD22 blockade also led to significantly reduced phosphorylation of SYK and GSK3β in NMOSD. Notably, the detrimental effects of CD22 blockade were greatly diminished in NMOSD mice receiving the phosphorylated SYK inhibitor R406. Conclusions Our findings revealed a previously unrecognized role of CD22 as a key molecular switch that governs the detrimental effects of microglia and Gr-1+ myeloid cells in NMOSD, which paves the way for the future design of immune therapies for NMOSD. Graphical abstracthttps://doi.org/10.1186/s12974-024-03305-2CD22MicrogliaNeuroinflammationNeuromyelitis optica spectrum disorderDemyelination |
| spellingShingle | Wenjun Zhang Yali Han Huachen Huang Yue Su Honglei Ren Caiyun Qi Jinyi Li Huaijin Yang Jing Xu Guoqiang Chang Wenjin Qiu Qiang Liu Ting Chang CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder Journal of Neuroinflammation CD22 Microglia Neuroinflammation Neuromyelitis optica spectrum disorder Demyelination |
| title | CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder |
| title_full | CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder |
| title_fullStr | CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder |
| title_full_unstemmed | CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder |
| title_short | CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder |
| title_sort | cd22 blockade exacerbates neuroinflammation in neuromyelitis optica spectrum disorder |
| topic | CD22 Microglia Neuroinflammation Neuromyelitis optica spectrum disorder Demyelination |
| url | https://doi.org/10.1186/s12974-024-03305-2 |
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