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

Author

Listed:
  • Ulrika Norin

    (Karolinska Institute)

  • Carola Rintisch

    (Karolinska Institute
    Lund University
    Max-Delbrück-Center for Molecular Medicine (MDC))

  • Liesu Meng

    (Karolinska Institute
    Xi’an Jiaotong University Health Science Center)

  • Florian Forster

    (Karolinska Institute)

  • Diana Ekman

    (Karolinska Institute
    Stockholm University)

  • Jonatan Tuncel

    (Karolinska Institute)

  • Katrin Klocke

    (Karolinska Institute)

  • Johan Bäcklund

    (Karolinska Institute)

  • Min Yang

    (Karolinska Institute)

  • Michael Y. Bonner

    (Karolinska Institute)

  • Gonzalo Fernandez Lahore

    (Karolinska Institute)

  • Jaime James

    (Karolinska Institute)

  • Klementy Shchetynsky

    (Karolinska Institute and Karolinska University Hospital)

  • Maria Bergquist

    (University of Gothenburg
    Uppsala University)

  • Inger Gjertsson

    (University of Gothenburg)

  • Norbert Hubner

    (Max-Delbrück-Center for Molecular Medicine (MDC)
    Charité-Universitätsmedizin Berlin)

  • Liselotte Bäckdahl

    (Karolinska Institute)

  • Rikard Holmdahl

    (Karolinska Institute
    Xi’an Jiaotong University Health Science Center)

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.

Suggested Citation

  • 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 & , 2021. "Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20586-2
    DOI: 10.1038/s41467-020-20586-2
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