Targeting Piezo1 Protein May Be An Ideal New Strategy To Cure Multiple Sclerosis

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In a new study from the University of California, Irvine, researchers found that a certain protein prevented regulatory T cells (Tregs) from doing their job effectively in controlling the damaging effects of inflammation in a model of sclerosis plaque (MS), a devastating autoimmune disease. nervous system disease.

Posted this month in Scientists progress, the new study highlights the important role of Piezo1, a specialized protein called the ion channel, in the immunity and function of T cells linked to autoimmune neuro-inflammatory disorders.

We found that Piezo1 selectively retains Treg cells, limiting their potential to attenuate autoimmune neuroinflammation. Genetic suppression of Piezo1 in transgenic mice resulted in an enlarged pool of Treg cells, which were more able to effectively reduce neuroinflammation and with it the severity of disease. “

Michael D. Cahalan, PhD, Emeritus Professor and Chairman, Department of Physiology and Biophysics, UCI Faculty of Medicine

T cells rely on specialized proteins, such as Piezo1, to detect and respond to a variety of diseases and conditions, including bacterial infections, wound healing, and even cancer. The uncontrolled activity of T cells, however, can give rise to autoimmune disorders in which the immune system attacks normal cells in the body. Tregs constantly heal immune responses and play an essential role in preventing autoimmunity.

“Given the demonstrated ability of Piezo1 to retain Treg cells, we believe that inhibition of Piezo1 could lead to new treatments for neuro-inflammatory disorders, such as MS,” explained Amit Jairaman, PhD, and Shivashankar Othy, PhD, principal authors of the study, both from the scientific project of the department of physiology and biophysics.

Piezo1 conducts ions when cells are subjected to mechanical forces. Research over the past decade has shed light on the role of Piezo1 in the regulation of vital physiological functions, including red blood cell volume (RBC), blood pressure, vascular development, bone formation, and cell differentiation. neural strains. However, its role in modulating the immune response has not been appreciated before. And, while calcium-conducting ion channels, like Piezo1, were known to direct various aspects of T cell function, researchers were surprised to find that Piezo1 was not essential for a host of cell functions. T cells that depend on calcium, such as lymph nodes. homing, interstitial motility, activation, proliferation or differentiation into effector T cells.

“We found that the role of Piezo1 appears to be quite specific to Tregs. Therefore, targeting Piezo1 could be an ideal new strategy for curing MS while preserving the ability of the immune system to fight new infections,” added Othy, whose research lasted 12 years. focused on finding ways to harness the therapeutic potential of Treg cells.

Further study of the function of Piezo1 is needed to understand the therapeutic potential and better understand the processes by which cells sense and respond to mechanical stimuli during immune responses.

Source:

Journal reference:

Jairman, A., et al. (2021) Piezo1 channels restrict regulatory T cells but are essential for effector CD4 + T cell responses. Scientists progress. doi.org/10.1126/sciadv.abg5859.


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