TY - JOUR
T1 - Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation
AU - Norin, Ulrika
AU - Rintisch, Carola
AU - Meng, Liesu
AU - Forster, Florian
AU - Ekman, Diana
AU - Tuncel, Jonatan
AU - Klocke, Katrin
AU - Bäcklund, Johan
AU - Yang, Min
AU - Bonner, Michael Y.
AU - Lahore, Gonzalo Fernandez
AU - James, Jaime
AU - Shchetynsky, Klementy
AU - Bergquist, Maria
AU - Gjertsson, Inger
AU - Hubner, Norbert
AU - Bäckdahl, Liselotte
AU - Holmdahl, Rikard
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-20586-2
DO - 10.1038/s41467-020-20586-2
M3 - Article
C2 - 33504785
AN - SCOPUS:85099923306
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 610
ER -
