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

Research output: Contribution to journalArticle


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.


  • 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
External organisations
  • Karolinska Institutet
  • Max Delbrück Center for Molecular Medicine (MDC)
  • Xi’an Medical University
  • Stockholm University
  • Karolinska University Hospital
  • Uppsala University
  • Charité - University Medicine Berlin
  • Second Affiliated Hospital of Xi'an Jiaotong University
  • University of Gothenburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity
Original languageEnglish
Article number610
JournalNature Communications
Issue number1
Publication statusPublished - 2021
Publication categoryResearch