NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis
Abstract Never in mitosis gene A (NIMA)-related kinase 2 (NEK2), a member of the serine-threonine kinase family, is critically involved in the regulation of the cell cycle. Upregulation of NEK2 is associated with aberrant B cell proliferation, a phenomenon potentially driven by NEK2-mediated disrupt...
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BMC
2025-06-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03472-w |
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| author | Si-Ting Wu Tian-Xiang Zhang Zhirui Liu Xueting An Xiaoshan Du Shu Yang Ti Wu Guanju Di Jingshi Song Bin Feng Chunyang Wang Chao Zhang |
| author_facet | Si-Ting Wu Tian-Xiang Zhang Zhirui Liu Xueting An Xiaoshan Du Shu Yang Ti Wu Guanju Di Jingshi Song Bin Feng Chunyang Wang Chao Zhang |
| author_sort | Si-Ting Wu |
| collection | DOAJ |
| description | Abstract Never in mitosis gene A (NIMA)-related kinase 2 (NEK2), a member of the serine-threonine kinase family, is critically involved in the regulation of the cell cycle. Upregulation of NEK2 is associated with aberrant B cell proliferation, a phenomenon potentially driven by NEK2-mediated disruption of the PKM1/PKM2 equilibrium. The overexpression of NEK2 in the B cell lineage may facilitate the maturation processes of B cells. Nonetheless, the precise role of NEK2 in modulating B cell-mediated immunity in autoimmune disorders remains to be fully elucidated. In this study, we demonstrate that NEK2 was significantly upregulated in multiple sclerosis (MS) patients. Pharmacological inhibition of NEK2 resulted in a marked reduction in the expression of co-stimulatory molecules CD80 and CD86 on B cells, concomitant with a suppression of their proliferation and differentiation into antibody-secreting cells (ASCs) and class-switched memory B cells (SWM). Administration of the NEK2 inhibitor INH1 in a murine model of experimental autoimmune encephalomyelitis (EAE) led to notable improvements in neurological function, amelioration of demyelination, and a decrease in the infiltration of inflammatory cells in the central nervous system (CNS) compared to vehicle-treated EAE mice. Mass cytometry analysis revealed that NEK2 inhibition downregulated the expression of co-stimulatory molecules and diminished the proportion of Th1 cells in the CD4 + T cell population. In vitro studies further substantiated that NEK2 blockade attenuated CD4 + T cell proliferation and differentiation into Th1 cells by disrupting B-T cell interactions. Collectively, these findings underscore an immunomodulatory function for NEK2 and highlight its potential as a therapeutic target in the treatment of multiple sclerosis. |
| format | Article |
| id | doaj-art-2903da4ba7b248abb4e01e74369bc96f |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-2903da4ba7b248abb4e01e74369bc96f2025-08-20T03:25:19ZengBMCJournal of Neuroinflammation1742-20942025-06-0122111410.1186/s12974-025-03472-wNEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitisSi-Ting Wu0Tian-Xiang Zhang1Zhirui Liu2Xueting An3Xiaoshan Du4Shu Yang5Ti Wu6Guanju Di7Jingshi Song8Bin Feng9Chunyang Wang10Chao Zhang11Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Scientific Research, Tianjin Medical University General HospitalDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General HospitalAbstract Never in mitosis gene A (NIMA)-related kinase 2 (NEK2), a member of the serine-threonine kinase family, is critically involved in the regulation of the cell cycle. Upregulation of NEK2 is associated with aberrant B cell proliferation, a phenomenon potentially driven by NEK2-mediated disruption of the PKM1/PKM2 equilibrium. The overexpression of NEK2 in the B cell lineage may facilitate the maturation processes of B cells. Nonetheless, the precise role of NEK2 in modulating B cell-mediated immunity in autoimmune disorders remains to be fully elucidated. In this study, we demonstrate that NEK2 was significantly upregulated in multiple sclerosis (MS) patients. Pharmacological inhibition of NEK2 resulted in a marked reduction in the expression of co-stimulatory molecules CD80 and CD86 on B cells, concomitant with a suppression of their proliferation and differentiation into antibody-secreting cells (ASCs) and class-switched memory B cells (SWM). Administration of the NEK2 inhibitor INH1 in a murine model of experimental autoimmune encephalomyelitis (EAE) led to notable improvements in neurological function, amelioration of demyelination, and a decrease in the infiltration of inflammatory cells in the central nervous system (CNS) compared to vehicle-treated EAE mice. Mass cytometry analysis revealed that NEK2 inhibition downregulated the expression of co-stimulatory molecules and diminished the proportion of Th1 cells in the CD4 + T cell population. In vitro studies further substantiated that NEK2 blockade attenuated CD4 + T cell proliferation and differentiation into Th1 cells by disrupting B-T cell interactions. Collectively, these findings underscore an immunomodulatory function for NEK2 and highlight its potential as a therapeutic target in the treatment of multiple sclerosis.https://doi.org/10.1186/s12974-025-03472-wNEK2Multiple sclerosisExperimental autoimmune encephalomyelitisB cells |
| spellingShingle | Si-Ting Wu Tian-Xiang Zhang Zhirui Liu Xueting An Xiaoshan Du Shu Yang Ti Wu Guanju Di Jingshi Song Bin Feng Chunyang Wang Chao Zhang NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis Journal of Neuroinflammation NEK2 Multiple sclerosis Experimental autoimmune encephalomyelitis B cells |
| title | NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis |
| title_full | NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis |
| title_fullStr | NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis |
| title_full_unstemmed | NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis |
| title_short | NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis |
| title_sort | nek2 regulates b cell function and the severity of experimental autoimmune encephalomyelitis |
| topic | NEK2 Multiple sclerosis Experimental autoimmune encephalomyelitis B cells |
| url | https://doi.org/10.1186/s12974-025-03472-w |
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