Tag: autoimmune disease

Categories : Immune SystemTags :

Newly Discovered ‘Goldilocks’ Protein Keeps the Immune System in Check

On By ModernMedia

A newly discovered ‘Goldilocks’ protein may be responsible for helping keep the immune system from running amok, according to researchers at the Lunenfeld-Tanenbaum Research Institute (LTRI).

This protein, known as WAVE2, is expressed in all immune cells and plays a critical role in keeping the immune system in balance. To test its role, researchers knocked out the WAVE2 protein in a subset of immune cells in mice, leading to severe autoimmunity and inflammation, as well as an inability to mount an immune response to a viral infection.

Senior author Dr Kathy Siminovitch, said the team also found that in the absence of WAVE2, another protein, known as mTOR, became overly active, sending the immune system into overdrive and leading to immune cell exhaustion.

“Much like Goldilocks, a proper immune response requires such a delicate balance,” said Dr  Siminovitch. “You have to get it just right. By developing a mouse strain in which T cells, key players in immunity, lack WAVE2, we have shown that this protein is absolutely required for balanced immune responses.”

The question of how to keep the immune system in balance is of key importance in the pandemic, where many deaths occur due to cytokine storms as the immune system overreacts, especially in the elderly. 
As part of her work exploring the mechanisms balancing the immune system, Dr Siminovitch helped trace the complex molecular steps that turn a rare gene mutation into Wiskott-Aldrich syndrome, a potentially lethal disease which impairs the immune system of boys.

Future research would look at how the contribution of the WAVE2-mTOR pathway to specific autoimmune, inflammatory and other conditions, such as Alzheimer’s disease.

Source: News-Medical.Net

Journal information: Liu, M., et al. (2021) WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity. Science. doi.org10.1126/science.aaz4544.

Categories : Diseases, Syndromes and Conditions T-cellsTags :

Ginger Promising in Countering Autoimmune Diseases

On By ModernMedia

A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385

Categories : Diseases, Syndromes and ConditionsTags :

Promising Drug May Worsen Instead of Treat Multiple Sclerosis

On By ModernMedia

A drug, TEPP-46,  that is being assessed to treat multiple sclerosis (MS) may in fact be worsening the progression of the disease, wrote University of Virginia on the Medical Xpress website.

MS is a debilitating disease which affects over one million people in America, in which the immune system attacks the myelin sheath, creating a range of effects in sufferers, from muscle spasms to numbness.

Presently available drugs to treat MS often have unwanted side effects, such as weakening the immune system. Originally developed to fight cancer, TEPP-46 is small-molecule drug that targets the changes in cellular metabolism that occur in both cancer and MS. However, the drug has been shown to produce off-target effects. In the mouse model used by the researchers, the inflammation was directed away from the spinal cord and into the brain. The researchers believed that this was the result of the drug harmfully changing T cells, but could not explain why. 

“It was not at all what we expected,” said MS researcher Alban Gaultier, PhD, of University of Virginia. “The take-home message is that we should be very careful and do more fundamental research before we propose to take this to clinical trials.”