New murine model sheds light on anti-MDA5 antibody-positive dermatomyositis

NewsGuard 100/100 Score

Some diseases involve autoimmune reactions, when the body begins to attack its own cells and proteins. The biological mechanisms underlying these diseases are often unknown, making treatment challenging. Now, a group at TMDU has created a murine model for a disease known as "anti-MDA5 antibody-positive dermatomyositis". Use of this model has allowed them to identify components of the immune system that are vital in disease development, with implications for future treatments.

Dermatomyositis is a member of a disease group known as idiopathic inflammatory myopathies, which cause typical rashes and muscle weakness, leading to disability and premature death. As part of the normal immune response, the body produces proteins known as antibodies, specific to individual "antigens", or foreign substances. However, autoimmune reactions involve the abnormal production of antibodies to human proteins, called "autoantibodies". Anti-MDA5 antibody-positive dermatomyositis involves the production of autoantibodies against the protein MDA5, causing rashes and lung inflammation and fibrosis, called interstitial lung disease (ILD). This often progresses very rapidly with a high mortality rate, and current anti-inflammatory treatments are ineffective.

To develop a model of this disease in mice, we first triggered the production of anti-MDA5 autoantibodies. This resulted in the development of some lung inflammation but not full ILD."

Dr. Yuki Ichimura, lead author of the study

Because MDA5 is involved in the body's response to certain viruses, the team then mimicked a viral infection in the lungs. The mice producing anti-MDA5 antibodies developed significant lung inflammation and fibrosis, emulating the pathogenesis seen in human patients, successfully modeling the disease.

The researchers then analyzed the specific immune responses occurring in the mice and investigated how these led to disease. Of the various cells involved in the immune response, they showed that cells called "CD4-positive T cells" are key for the development of ILD. Experimentally reducing the numbers of these cells lessened the lung damage observed. The involvement of these T cells is backed up by autopsy findings from the lungs of patients.

The research team went on to identify elevated levels of a signaling molecule called interleukin-6 in the murine model. "Experimental reduction of interleukin-6 levels ameliorated the development of ILD," explains senior author Dr. Naoko Okiyama, "indicating that medical intervention targeting interleukin-6 could be a potential treatment option for ILD."

The murine model developed in this study provides a key tool for investigating the mechanisms underlying anti-MDA5 antibody-positive dermatomyositis, the value of which is proved by the identification of key factors in the immune system involved in this highly progressive disease. Future work enabled by this study could aid in the development of more specific and effective therapies, improving treatment and quality of life.

Journal reference:

Ichimura, Y., et al. (2024). Autoimmunity against melanoma differentiation–associated gene 5 induces interstitial lung disease mimicking dermatomyositis in mice. Proceedings of the National Academy of Sciences.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Bats in China found to carry novel herpesviruses, hinting at cross-species transmission dangers