| Literature DB >> 33504785 |
Ulrika Norin1, Carola Rintisch2,3,4, Liesu Meng2,5, Florian Forster2, Diana Ekman2,6, Jonatan Tuncel2, Katrin Klocke2, Johan Bäcklund2, Min Yang2, Michael Y Bonner2, Gonzalo Fernandez Lahore2, Jaime James2, Klementy Shchetynsky7, Maria Bergquist8,9, Inger Gjertsson8, Norbert Hubner4,10, Liselotte Bäckdahl2, Rikard Holmdahl11,12.
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.Entities:
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Year: 2021 PMID： 33504785 DOI： 10.1038/s41467-020-20586-2
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919