TARM1 is a receptor protein, whose function in the working of the immune system is not known yet. Now, in new research work, Japanese researchers have analyzed mouse models to investigate the promising role of TARM1 protein in the pathogenesis of rheumatoid arthritis.
Immune Receptor Protein Could Hold Key to Treatment of Autoimmune Diseases
Scientists show how a receptor protein plays a role in the immune response, yielding a potential therapeutic target for diseases like rheumatoid arthritis. Video Credit: Tokyo University of Science.
The researchers observed that the TARM1 protein stimulated dendritic cells and that the development of collagen-induced arthritis (CIA) was considerably inhibited in TARM1-deficient mice and also when treated with TARM1-inhibitory soluble TARM1 proteins. As a result, the protein could offer a promising therapeutic target.
Autoimmune diseases are usually triggered when the immune system, whose role is to tackle foreign threats to the body, mistakenly identifies the body’s own cells and proteins as threats and stimulates immune cells to fight them.
With regard to rheumatoid arthritis, which is a familiar autoimmune condition, immune cells wrongly target the body’s own proteins and joint components, leading to intolerable inflammation and even the destruction of bones.
With these findings in recent research work, Japanese researchers have now taken a major step toward interpreting and possibly treating rheumatoid arthritis in a more effective way. The study has demonstrated these possibilities below.
The emergence of autoimmune disorders is a remarkably complex process that involves many key players, such as environmental and genetic factors. Dendritic cells (DCs), which stimulate the immune response against infections, are one of the primary immune cells implicated in the pathogenesis of autoimmune disorders.
All immune cells, such as DCs, contain a wide range of receptors on their surfaces that can either inhibit or amplify the immune response. T cell-interacting, activating receptor on myeloid cells-1 (TARM1) is one such receptor.
TARM1 belongs to the family of leukocyte immunoglobulin-like receptors and supports the stimulation of other immune cells, like macrophages and neutrophils. The functions of the TARM1 indicate that it may play a key role in the immune response, but the viability of its role in the pathogenesis of rheumatoid arthritis is yet to be fully investigated.
The afore-mentioned research team, headed by Professor Yoichiro Iwakura of Tokyo University of Science and Rikio Yabe and Shinobu Saijo of Chiba University, wanted to learn more about this relationship.
In their research work, recently published in the Nature Communications journal, the team identified genes that were overexpressed in numerous mouse models of arthritis. Fascinatingly, TARM1was found to be one of many such genes.
Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in TARM1-deficient mice.”
Yoichiro Iwakura, Professor, Tokyo University of Science
The response of the immune system to type 2 collagen (IIC)—a protein necessary for the development of CIA in mice, was inhibited in TARM1-deficient mice, observed by the researchers. They also discovered that the antigen-presenting capacity of DCs was impaired in the TARM1-deficient mice.
With regard to the significance of these results, Professor Iwakura explained, “We have shown that TARM1 plays an important role for the maturation and activation of DCs through interaction with IIC.”
The researchers finally administrated TARM1-inhibitory soluble TARM1 proteins into the knee of a mouse affected by the CIA. Most importantly, this inhibited the development of CIA in mice, implying that TARM1 inhibition was effective in weakening autoimmune arthritis.
The researchers’ discoveries about the TARM1 protein have far-reaching consequences for treating rheumatoid arthritis and also other allergic and autoimmune diseases.
Commenting on their crucial discoveries, Professor Iwakura stated, “Because excess DC activation is suggested in many autoimmune and allergic diseases, our observations suggest that TARM1 is a good target for the development of new drugs to treat such diseases.”
The results of this groundbreaking research work clearly demonstrate that there is still more to understand about autoimmune disorders, such as rheumatoid arthritis, and the more researchers learn about these disorders, the better they can deal with them.
Yabe, R., et al. (2021) TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens. Nature Communications. doi.org/10.1038/s41467-020-20307-9.