ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation
Summary: Proteasomes generate antigenic peptides presented on cell surfaces—a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-anti...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015122 |
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| author | Sheng-Wen Chen Ying Chu Chien-Hsin Chu Xuan-Dieu Thi Pham Hang Pong Ng Chin-Lin Guo Pei-Lin Cheng |
| author_facet | Sheng-Wen Chen Ying Chu Chien-Hsin Chu Xuan-Dieu Thi Pham Hang Pong Ng Chin-Lin Guo Pei-Lin Cheng |
| author_sort | Sheng-Wen Chen |
| collection | DOAJ |
| description | Summary: Proteasomes generate antigenic peptides presented on cell surfaces—a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations. We demonstrate that loss of the proteasome adaptor protein Ecm29 alters the efficacy and accuracy of antigen generation. Inducible oligodendroglia- or microglia-conditional Ecm29 knockout mice exhibit higher susceptibility to experimental autoimmune encephalomyelitis (EAE) than control counterparts do, coincident with reduced Treg cell populations in the spinal cord. Immunopeptidome profiling identifies self-antigens that modulate myelin-reactive T cell responses. Intraspinal adeno-associated virus (AAV)/Olig001-mediated expression of the self-antigen NDUFA1p ameliorates EAE and expands NDUFA1p-recognizing CD103+CD8+CD122+ Treg cells. Thus, Ecm29/proteasome-controlled, neuroglia-derived self-antigens modulate CNS immune tolerance. |
| format | Article |
| id | doaj-art-96a9873e43504bdc8b4200b9ed74a8e4 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-96a9873e43504bdc8b4200b9ed74a8e42025-01-09T06:13:49ZengElsevierCell Reports2211-12472025-01-01441115161ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activationSheng-Wen Chen0Ying Chu1Chien-Hsin Chu2Xuan-Dieu Thi Pham3Hang Pong Ng4Chin-Lin Guo5Pei-Lin Cheng6Institute of Molecular Biology, Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei, TaiwanInstitute of Physics, Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan; Corresponding authorSummary: Proteasomes generate antigenic peptides presented on cell surfaces—a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations. We demonstrate that loss of the proteasome adaptor protein Ecm29 alters the efficacy and accuracy of antigen generation. Inducible oligodendroglia- or microglia-conditional Ecm29 knockout mice exhibit higher susceptibility to experimental autoimmune encephalomyelitis (EAE) than control counterparts do, coincident with reduced Treg cell populations in the spinal cord. Immunopeptidome profiling identifies self-antigens that modulate myelin-reactive T cell responses. Intraspinal adeno-associated virus (AAV)/Olig001-mediated expression of the self-antigen NDUFA1p ameliorates EAE and expands NDUFA1p-recognizing CD103+CD8+CD122+ Treg cells. Thus, Ecm29/proteasome-controlled, neuroglia-derived self-antigens modulate CNS immune tolerance.http://www.sciencedirect.com/science/article/pii/S2211124724015122CP: NeuroscienceCP: Immunology |
| spellingShingle | Sheng-Wen Chen Ying Chu Chien-Hsin Chu Xuan-Dieu Thi Pham Hang Pong Ng Chin-Lin Guo Pei-Lin Cheng ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation Cell Reports CP: Neuroscience CP: Immunology |
| title | ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation |
| title_full | ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation |
| title_fullStr | ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation |
| title_full_unstemmed | ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation |
| title_short | ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation |
| title_sort | ecm29 proteasome mediated self antigen generation by cns resident neuroglia promotes regulatory t cell activation |
| topic | CP: Neuroscience CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015122 |
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