Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation
| Autor: | Jonatan Tuncel, Florian Forster, Klementy Shchetynsky, Liselotte Bäckdahl, Liesu Meng, Inger Gjertsson, Norbert Hubner, Rikard Holmdahl, Michael Y. Bonner, Johan Bäcklund, Ulrika Norin, Min Yang, Jaime James, Katrin Klocke, Maria Bergquist, Gonzalo Fernandez Lahore, Diana Ekman, Carola Rintisch |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male T-Lymphocytes General Physics and Astronomy Arthritis Autoimmunity medicine.disease_cause Lymphocyte Activation Jurkat cells Arthritis Rheumatoid Jurkat Cells Mice 0302 clinical medicine Receptor Multidisciplinary Endocytosis Cell biology Up-Regulation medicine.anatomical_structure Female Signal transduction Signal Transduction Science T cell Adaptive immunity Receptors Antigen T-Cell T cells Biology General Biochemistry Genetics and Molecular Biology Article Autoimmune Diseases 03 medical and health sciences Downregulation and upregulation medicine Animals Humans Rheumatology and Autoimmunity 030203 arthritis & rheumatology Reumatologi och inflammation T-cell receptor Immunology in the medical area General Chemistry medicine.disease Rats 030104 developmental biology Cardiovascular and Metabolic Diseases Immunologi inom det medicinska området Mutation Lymph Nodes Acyltransferases |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) |
| Popis: | 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. The autoimmune disorder, rheumatoid arthritis (RA), has been associated with multiple pathophysiological factors. Here the authors show that deficiency in endophilin A2 in rodents protects them from experimental arthritis by altering T cell activation threshold and effector functions, thereby hinting a potential target for RA therapy. |
| Databáze: | OpenAIRE |
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