A recent review examines mast cells, the key immune cells involved in systemic mastocytosis (SM), and highlights how their diversity, shaped by a range of factors, makes them difficult to study.
The study, published in Pharmacological Reviews, summarizes decades of research on mast cells and the wide range of mediators they release — molecules that carry out many different biological functions in the body.
Mast cells begin in the bone marrow and enter the bloodstream in an immature form, finishing their development only after they settle into the body’s tissues. They reside throughout the body, including in the lungs, gut and skin, where they help defend against microbes and toxins. Each mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. can store up to 1,000 tiny packets, called granules, that hold mediators.
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Among the mediators are proteases, a type of enzyme that cuts other proteins to switch biological signals on or off; the review calls them “molecular scissors.”
When mast cells are triggered as intended, this activity supports the body’s defenses. But when mast cells build up or become overactive, as happens in SM, mast cell mediators can cause symptoms and damage.
Mast cells are also difficult to study because they are not uniform. Their properties and functions vary considerably depending on the tissue in which they reside, and they can alter their protease content during inflammation and later return to their earlier state. One large study mentioned in the review identified at least six distinct groups of human mast cells, each concentrated in specific organs.
Researchers also classify human and mouse mast cells using different criteria, which makes findings harder to compare across studies. Mouse and human mast cells also differ in important ways and develop under different conditions, so results from animal studies do not always apply to people. On the other hand, lab-grown mast cells do not fully match those found in the body, and different laboratory methods can yield cells with different features.
To work around these obstacles, the authors highlighted newer research tools. One is single-cell sequencing, which lets scientists read the genetic activity of individual cells one at a time. Another is the use of lab-grown “organoids,” miniature tissue models that mimic how cells behave inside the body.
The researchers also pointed to carboxypeptidase A3 (CPA3), a protease whose gene is highly active in the bone marrow cells of people with SM. Researchers are studying whether it could serve as a biomarker, a measurable sign that could help detect or monitor the disease.
Together, these approaches could help researchers map mast cell diversity more accurately and, over time, support better clinical trials and the development of individualized treatments.
Read more about mediators: “What people with mastocytosis should know about mast cell mediators”
