Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation

Ulrika Norin, Carola Rintisch, Liesu Meng, Florian Forster, Diana Ekman, Jonatan Tuncel, Katrin Klocke, Johan Bäcklund, Min Yang, Michael Y. Bonner, Gonzalo Fernandez Lahore, Jaime James, Klementy Shchetynsky, Maria Bergquist, Inger Gjertsson, Norbert Hubner, Liselotte Bäckdahl, Rikard Holmdahl

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Artikelnummer610
TidskriftNature Communications
Volym12
Utgåva1
DOI
StatusPublished - 2021

Ämnesklassifikation (UKÄ)

  • Reumatologi och inflammation

Fingeravtryck

Utforska forskningsämnen för ”Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här