Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation
Abstract Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory myopathy with invasion of CD8 T cells in muscle and aggregation of proteins in the sarcoplasm. TDP-43 and p62 are two proteins that aggregate in affected muscle, and have been suggested as specific markers for sIBM over o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-42824-5 |
| _version_ | 1797453026847358976 |
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| author | Bryony McCord Richard M. Day |
| author_facet | Bryony McCord Richard M. Day |
| author_sort | Bryony McCord |
| collection | DOAJ |
| description | Abstract Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory myopathy with invasion of CD8 T cells in muscle and aggregation of proteins in the sarcoplasm. TDP-43 and p62 are two proteins that aggregate in affected muscle, and have been suggested as specific markers for sIBM over other inflammatory myopathies. TDP-43 is also mislocalised from the nucleus to the sarcoplasm in sIBM. It is not clear if inflammation precedes protein aggregation in sIBM. This study investigated if exposure to cytotoxic inflammatory cells caused TDP-43 and p62 aggregation or TDP-43 mislocalisation in cultured myotubes. TALL-104 coculture was highly cytotoxic to myotubes after 24 h. Secretion of IFNγ and TNFα were higher in cocultures compared to monocultured TALL-104 cells, indicating activation. TALL-104 cells attached to and infiltrated myotubes. There was no effect of TALL-104 coculture on TDP-43 or p62 sarcoplasmic aggregate size or frequency. However, there was decreased localisation of TDP-43 to the nucleus with TALL-104 coculture compared to control. In an in vitro setting, cytotoxic immune cells did not cause TDP-43 or p62 sarcoplasmic aggregation, suggesting cellular cytotoxicity may not trigger aggregation of these proteins. However TALL-104 coculture influenced TDP-43 localisation, suggesting cytotoxic immune cells may contribute to TDP-43 localisation shifts which is observed in sIBM. |
| first_indexed | 2024-03-09T15:16:57Z |
| format | Article |
| id | doaj.art-c3723a8aab2a4508ba424775cd6aab4e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:16:57Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c3723a8aab2a4508ba424775cd6aab4e2023-11-26T13:04:04ZengNature PortfolioScientific Reports2045-23222023-09-0113111210.1038/s41598-023-42824-5Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisationBryony McCord0Richard M. Day1Centre for Precision Healthcare, UCL Division of Medicine, University College LondonCentre for Precision Healthcare, UCL Division of Medicine, University College LondonAbstract Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory myopathy with invasion of CD8 T cells in muscle and aggregation of proteins in the sarcoplasm. TDP-43 and p62 are two proteins that aggregate in affected muscle, and have been suggested as specific markers for sIBM over other inflammatory myopathies. TDP-43 is also mislocalised from the nucleus to the sarcoplasm in sIBM. It is not clear if inflammation precedes protein aggregation in sIBM. This study investigated if exposure to cytotoxic inflammatory cells caused TDP-43 and p62 aggregation or TDP-43 mislocalisation in cultured myotubes. TALL-104 coculture was highly cytotoxic to myotubes after 24 h. Secretion of IFNγ and TNFα were higher in cocultures compared to monocultured TALL-104 cells, indicating activation. TALL-104 cells attached to and infiltrated myotubes. There was no effect of TALL-104 coculture on TDP-43 or p62 sarcoplasmic aggregate size or frequency. However, there was decreased localisation of TDP-43 to the nucleus with TALL-104 coculture compared to control. In an in vitro setting, cytotoxic immune cells did not cause TDP-43 or p62 sarcoplasmic aggregation, suggesting cellular cytotoxicity may not trigger aggregation of these proteins. However TALL-104 coculture influenced TDP-43 localisation, suggesting cytotoxic immune cells may contribute to TDP-43 localisation shifts which is observed in sIBM.https://doi.org/10.1038/s41598-023-42824-5 |
| spellingShingle | Bryony McCord Richard M. Day Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation Scientific Reports |
| title | Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation |
| title_full | Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation |
| title_fullStr | Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation |
| title_full_unstemmed | Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation |
| title_short | Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation |
| title_sort | cytotoxic immune cells do not affect tdp 43 and p62 sarcoplasmic aggregation but influence tdp 43 localisation |
| url | https://doi.org/10.1038/s41598-023-42824-5 |
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