Open this publication in new window or tab >>Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden.;Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.
Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden..
Max Delbruck Ctr Mol Med MDC, Cardiovasc & Metab Sci, Berlin, Germany.;Charite Univ Med Berlin, Berlin, Germany..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden.;Xi An Jiao Tong Univ, Affiliated Hosp 2, Xian 710061, Shaanxi, Peoples R China.;Xi An Jiao Tong Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Sch Basic Med Sci, Xian 710061, Shaanxi, Peoples R China..
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2021 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 12, no 1, article id 610Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2021
National Category
Rheumatology and Autoimmunity Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-441388 (URN)10.1038/s41467-020-20586-2 (DOI)000614500600010 ()33504785 (PubMedID)
2021-05-032021-05-032024-01-15Bibliographically approved