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

Norin, Ulrika ; Rintisch, Carola LU ; Meng, Liesu ; Forster, Florian ; Ekman, Diana ; Tuncel, Jonatan LU ; Klocke, Katrin ; Bäcklund, Johan LU ; Yang, Min and Bonner, Michael Y. , et al. (2021) In Nature Communications 12(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
610
publisher
Nature Publishing Group
external identifiers
  • scopus:85099923306
  • pmid:33504785
ISSN
2041-1723
DOI
10.1038/s41467-020-20586-2
language
English
LU publication?
yes
id
928b2656-cc12-446f-9ee7-a530e1214d19
date added to LUP
2021-02-05 11:08:36
date last changed
2022-05-24 04:34:26
@article{928b2656-cc12-446f-9ee7-a530e1214d19,
  abstract     = {{<p>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.</p>}},
  author       = {{Norin, Ulrika and Rintisch, Carola and Meng, Liesu and Forster, Florian and Ekman, Diana and Tuncel, Jonatan and Klocke, Katrin and Bäcklund, Johan and Yang, Min and Bonner, Michael Y. and Lahore, Gonzalo Fernandez and James, Jaime and Shchetynsky, Klementy and Bergquist, Maria and Gjertsson, Inger and Hubner, Norbert and Bäckdahl, Liselotte and Holmdahl, Rikard}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation}},
  url          = {{http://dx.doi.org/10.1038/s41467-020-20586-2}},
  doi          = {{10.1038/s41467-020-20586-2}},
  volume       = {{12}},
  year         = {{2021}},
}