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| Item Type: | Article |
|---|---|
| Title: | Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation |
| Creators Name: | Norin, U., Rintisch, C., Meng, L., Forster, F., Ekman, D., Tuncel, J., Klocke, K., Bäcklund, J., Yang, M., Bonner, M.Y, Lahore, G.F., James, J., Shchetynsky, K., Bergquist, M., Gjertsson, I., Hubner, N., Bäckdahl, L. and Holmdahl, R. |
| Abstract: | The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that a mutation in the SH3gl1 gene encoding the endocytic protein Endophilin A2 is associated with the development of arthritis in rodents. Defective expression of SH3gl1 affects T cell effector functions and alters the activation threshold of autoreactive T cells, thereby leading to complete protection from chronic autoimmune inflammatory disease in both mice and rats. We further show that SH3GL1 regulates human T cell signaling and T cell receptor internalization, and its expression is upregulated in rheumatoid arthritis patients. Collectively our data identify SH3GL1 as a key regulator of T cell activation, and as a potential target for treatment of autoimmune diseases. |
| Keywords: | Acyltransferases, Autoimmune Diseases, Autoimmunity, Endocytosis, Jurkat Cells, Lymph Nodes, Lymphocyte Activation, Mutation, Rheumatoid Arthritis, Signal Transduction, T-Cell Antigen Receptors, T-Lymphocytes, Up-Regulation, Animals, Mice, Rats |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 12 |
| Number: | 1 |
| Page Range: | 610 |
| Date: | 27 January 2021 |
| Official Publication: | https://doi.org/10.1038/s41467-020-20586-2 |
| PubMed: | View item in PubMed |
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