By targeting the iron metabolism of immune system cells, specialists may provide a new treatment method for systemic lupus erythematosus (SLE), which is the most prevalent form of the autoimmune disease lupus.
Inhibiting Iron Uptake Receptor Decreases Lupus Pathology, Boosts Anti-Inflammatory Cell Activity
According to Technology Networks, an investigating team comprising multidisciplinary specialists has found out that inhibiting the receptor for iron uptake decreases the pathology of the condition and boosts anti-inflammatory regulatory T cell activity in an SLE mouse model.
Their findings were included in the Science Immunology publication.
SLE and other kinds of lupus take place when one's immune system attacks the person's very own tissues that are healthy. This leads to pain, tissue damage, and inflammation.
In most cases, lupus affects the joints, skin, brain, kidneys, blood vessels, and lungs. Technology Networks reports that around 1.5 million Americans and 5 million individuals from all over the world have some kind of lupus.
Lupus treatments primarily aim to control and manage symptoms, decrease the attack of the immune system upon tissues, and protect against organ damage. Technology Networks also reports that there is only one specific targeted biologic agent that has gained approval for SLE treatment since 2011. This is belimumab.
Challenges in Developing Novel Lupus Treatments
That being said, professor and chairperson Jeffrey Rathmell, PhD, notes how it has been a huge challenge to come up with novel lupus therapies.
He notes how the disease and its patient population are both heterogeneous. This makes it difficult for them to come up with and perform clinical trials.
Observed Heightened Iron Levels
Science Daily reports how Rathmell's team has been interested in lupus in their general endeavors to know more about autoimmunity mechanisms.
When Kelsey Voss, PhD, postdoctoral fellow and study author, started studying the metabolisms of T cells in lupus, she observed that iron was a common denominator among the various issues within T cells. She also found it intriguing how the iron levels in the T cells of lupus patients were higher, even if these patients had anemia as well.
Voss notes that the reasons behind the heightened iron levels are not clear.
To dive further into the iron metabolism within T cells among those with lupus, Rathmell and Voss garnered expert assistance from other investigators from the Vanderbilt University Medical Center.
Technology Networks report how Voss first used a "CRISPR genome editing screen" in order to examine the genes that handle iron in the T cells. Voss was able to pinpoint the transferring receptor, which is in charge of importing the iron into the cells, as a vital player when it comes to T cell inflammation and as an inhibitor for anti-inflammatory regulatory T cells.
The investigators discovered that the transferrin receptor has higher expression in the T cells among the mice that were prone to developing SLE as well as in the patients with SLE. This led to too much iron accumulation.
Voss notes how various complications result from this. For one, the mitochondria do not properly function, and certain pathway signals also get changed.
Antibody That Targets the Transferrin Receptor Decreased Iron Levels, Blocked Inflammatory Activity, and Enhanced Regulatory Activity
Technology Networks reports how a specific antibody that inhibits the transferrin receptor significantly decreased intracellular iron levels, blocked inflammatory activity within T cells, and boosted regulatory activity within T cells. Treating the mice that were prone to SLE with the antibody led to decreased pathologies for the kidney and liver and increased creation of the anti-inflammatory factor, IL-10.
Voss notes that by targeting an autoimmune condition by impacting the function of its T cells, it is an option to block inflammatory T cells but not endanger regulatory T cells. This is what happened when the transferrin receptor was indeed targeted.
Among patients with lupus, transferrin receptor expression was correlated with the severity of the disease. In vitro blocking of the receptor boosted IL-10 production.
The investigators are interested in coming up with antibodies for transferrin receptors that specifically bind with T cells. They would also like to look deeper into these findings.
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