There are no cures for autoimmune disorders. However, researchers have made progress in managing symptoms and are seeking more new potential therapeutic targets and insights into treatment. Now, researchers at the Medical University of Vienna have discovered an immunoregulatory protein that could be linked to the development of autoimmune diseases such as rheumatoid arthritis.
The findings are published in the Journal of Experimental Medicine in an article titled, “The guanine nucleotide exchange factor Rin-like controls Tfh cell differentiation via CD28 signaling.”
“T follicular helper (Tfh) cells are essential for the development of germinal center B cells and high-affinity antibody-producing B cells in humans and mice. Here, we identify the guanine nucleotide exchange factor (GEF) Rin-like (Rinl) as a negative regulator of Tfh generation. Loss of Rinl leads to an increase of Tfh in aging, upon in vivo immunization and acute LCMV Armstrong infection in mice, and in human CD4+ T cell in vitro cultures.”
“By analyzing mouse models and cultures of human T cells, we have discovered that Rinl controls the development of follicular T helper cells, the Tfh,” said study leaders Nicole Boucheron, PhD, group leader, and Ruth Herbst, PhD, associated professor, both at the Medical University of Vienna. Tfh are a subset of T cells and support the maturation of other essential components of the immune system, the B cells. Mature B cells, in turn, produce highly effective 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 the body’s own body and damage it. “Our study reveals the previously unknown mechanism of how Rinl controls the development of Tfh cells in various immunological reactions, such as during a viral infection or during a vaccination,” explained first author Lisa Sandner, PhD, a former PhD student at the Medical University of Vienna.
As the researchers’ investigations of patient data from public databases also showed, there is a low concentration of Rinl proteins in the T cells of rheumatoid arthritis (RA). Based on these results, the protein may represent a new target for the development of immunomodulatory therapies for RA: “Pharmacotherapies that control Rinl and Rinl-dependent signaling pathways could help alleviate the symptoms of RA,” Boucheron said.
Interventions that inhibit Rinl could be used in immunodeficiency to help the body fight disease. Further research is needed to confirm the results and show whether the Rinl protein can also open up new therapy options for other diseases that are associated with a disturbed immune response, particularly in the regulation of Tfh cells.