Eiki Shirasawa, Kentaro Uchida, Kenji Onuma, Gen Inoue, Koji Eshima, Masashi Satoh, Masayuki Miyagi, Yoji Toyomura, Akira Norisugi, Masashi Takaso
{"title":"β2-微球蛋白调节周围神经损伤时细胞外基质动力学。","authors":"Eiki Shirasawa, Kentaro Uchida, Kenji Onuma, Gen Inoue, Koji Eshima, Masashi Satoh, Masayuki Miyagi, Yoji Toyomura, Akira Norisugi, Masashi Takaso","doi":"10.3390/neurosci6030059","DOIUrl":null,"url":null,"abstract":"<p><p>Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8<sup>+</sup> T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3<sup>+</sup>CD4<sup>+</sup> and CD3<sup>+</sup>CD8<sup>+</sup> T-cell populations increased by day 7 post-injury. While CD3<sup>+</sup>CD4<sup>+</sup> T-cell expansion occurred in both groups, a significant increase in CD3<sup>+</sup>CD8<sup>+</sup> T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury-prior to substantial T-cell accumulation-revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM-receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8<sup>+</sup> T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M's function beyond classical immune roles.</p>","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"6 3","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286088/pdf/","citationCount":"0","resultStr":"{\"title\":\"β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.\",\"authors\":\"Eiki Shirasawa, Kentaro Uchida, Kenji Onuma, Gen Inoue, Koji Eshima, Masashi Satoh, Masayuki Miyagi, Yoji Toyomura, Akira Norisugi, Masashi Takaso\",\"doi\":\"10.3390/neurosci6030059\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8<sup>+</sup> T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3<sup>+</sup>CD4<sup>+</sup> and CD3<sup>+</sup>CD8<sup>+</sup> T-cell populations increased by day 7 post-injury. While CD3<sup>+</sup>CD4<sup>+</sup> T-cell expansion occurred in both groups, a significant increase in CD3<sup>+</sup>CD8<sup>+</sup> T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury-prior to substantial T-cell accumulation-revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM-receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8<sup>+</sup> T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M's function beyond classical immune roles.</p>\",\"PeriodicalId\":74294,\"journal\":{\"name\":\"NeuroSci\",\"volume\":\"6 3\",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-06-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286088/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NeuroSci\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/neurosci6030059\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NeuroSci","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/neurosci6030059","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.
Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8+ T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3+CD4+ and CD3+CD8+ T-cell populations increased by day 7 post-injury. While CD3+CD4+ T-cell expansion occurred in both groups, a significant increase in CD3+CD8+ T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury-prior to substantial T-cell accumulation-revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM-receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8+ T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M's function beyond classical immune roles.