Autoimmune diseases: Protein discovered as potential new target for therapies

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Autoimmune diseases are complex conditions whose causes are diverse and have not been fully elucidated to date. A research team at MedUni Vienna has now discovered an immunoregulatory protein that could be linked to the development of autoimmune diseases such as rheumatoid arthritis. -Rinl- is the name of the identified building block of the immune system, which may provide a new starting point for the development of immunomodulatory therapies. The study results were recently published in the Journal of Experimental Medicine.

In the course of their research, the team led by Nicole Boucheron and Ruth Herbst (Center for Pathophysiology, Infectiology and Immunology at MedUni Vienna) found particularly high levels of Rinl in special immune cells, the T cells. Rinl, like its siblings Rin 1-3, is a member of the family of Ras-interacting proteins (Rin) and is a comparatively young object of research. While a deficiency or excess of Rin 1-3 proteins has already been linked in recent years in international studies, for example, to cancer, Alzheimer’s disease or the spinal disease scoliosis, Rinl has so far been little researched.

Mechanism in the immune system deciphered

The function of this protein in the immune system was clarified by the scientific team in the current study. -By analyzing mouse models and cultures of human T cells, we found that Rinl controls the development of follicular T’helper cells, or Tfh cells,- say study leaders Nicole Boucheron and Ruth Herbst. Tfh cells are a subset of T cells and support the maturation of other essential components of the immune system, B cells. Mature B cells, in turn, produce highly potent antibodies and thus play a major role in the body’s immune response: in vaccinations, a large amount of such antibodies is desired, but in autoimmune diseases such as rheumatoid arthritis (RA), they turn against and damage the body’s own immune system. -Our study reveals the previously unknown mechanism of how Rinl controls the development of Tfh cells in various immunological reactions, such as a viral infection or during a vaccination,- explains first author Lisa Sandner.

In addition, the researchers’ studies of patient data from public databases showed that a low concentration of Rinl proteins is present in T cells in RA. Based on these results, Rinl may represent a new target for the development of immunomodulatory therapies in RA: -Pharmacotherapies that control Rinl and Rinl-dependent signaling pathways could help alleviate the symptoms of RA-, Nicole Boucheron looks to the future. Conversely, interventions that inhibit Rinl could be used in immune deficiency to help the body fight disease. Further research should confirm the results and show whether the Rinl protein can also open up new therapeutic options for other diseases associated with a disturbed immune response (especially impaired regulation of Tfh cells).

Publication: Journal of Experimental Medicine

The guanine nucleotide exchange factor Rin-like controls Tfh cell differentiation via CD28 signaling Lisa Sandner, Marlis Alteneder, Ramona Rica, Barbara Woller, Eleonora Sala, Tobias Frey, Anela Tosevska, Ci Zhu, Moritz Madern, Matarr Khan, Pol Hoffmann, Alexandra Schebesta, Ichiro Taniuchi, Michael Bonelli, Klaus Schmetterer, Matteo Iannacone, Mirela Kuka, Wilfried Ellmeier, Shinya Sakaguchi, Ruth Herbst and Nicole Boucheron JEM 11-06-2023 issue, vol. 220 no. 11
https://doi.org/10.1084/je­m.20221466