New hope for allergic diseases: Shi Yigong's team's new discovery published in Nature

A-choo! Whether it’s the sound of sneezes coming one after another or the red rashes that come and go, more and more people are suffering from allergic diseases.

Allergy is also listed by the World Health Organization as one of the three major diseases that require key research and prevention in the 21st century.

Recently, a new study conducted by Shi Yigong's team from Westlake University and Su Qiang's team from Shenzhen Academy of Medical Sciences may bring new hope to people who are "helpless" in dealing with allergies.

At 23:00 Beijing time on October 23, 2024, the research paper titled "Molecular mechanism of IgE-mediated high-affinity receptor activation" was published in Nature.

This study reported for the first time the dimerization structure of the human core immunoglobulin IgE high affinity receptor (FcεRI), and through a variety of biochemical, cellular and flow cytometry experiments, demonstrated that IgE binding can induce the receptor to transform from a dimer to a monomer, and revealed the effect of this conformational change on receptor activation.

This discovery not only provides important insights into understanding the key mechanisms of IgE-FcεRI in allergic reactions, but also opens up new directions for the development of novel anti-allergic therapies.

Paper address: https://www.nature.com/articles/s41586-024-08229-8

Schematic diagram of IgE-mediated allergic reactions

IgE is the core immunoglobulin of allergic reactions, and its interaction with the high-affinity receptor FcεRI is crucial. Previous studies have shown that allergens induce cross-linking of IgE-bound FcεRI, causing mast cell degranulation and promoting the occurrence of allergic diseases. Drugs that target and destroy the binding of IgE to FcεRI are considered to be an effective anti-allergic treatment strategy.

Although the recognition mechanism of IgE and FcεRI has been studied relatively clearly, the research on the transmembrane region of FcεRI has been relatively weak. Studies have shown that the binding of IgE to FcεRI not only affects receptor activation, but also affects the survival, differentiation and maturation of mast cells, while the specific molecular mechanism of IgE-induced FcεRI activation is still unclear.

In this study, the team designed a series of experiments, combining biochemical, cell and immune techniques, revealing that FcεRI exists as a dimer under physiological conditions. Subsequent studies have shown that the dimerization of FcεRI is further carried out in cells by α and γ subunits. The research team confirmed through in vitro biochemical and in vivo cell experiments that IgE binding can induce FcεRI to transform from a dimer state to a monomeric form.

The binding of IgE is like a key that becomes the key to opening the dimer. The team proposed a working model for IgE-mediated activation of the FcεRI complex, which provides a new perspective for understanding the interaction between IgE and FcεRI and its role in allergic reactions.

The study was highly praised by the reviewers, who believed that the discovery of FcεRI dimers provided key mechanistic insights into the functional studies of IgE-FcεRI and praised this work for laying an important foundation for future research on anti-allergic therapies. This breakthrough discovery not only provides a new perspective for understanding the pathogenesis of allergic diseases, but also provides a scientific basis for developing therapeutic strategies targeting IgE-FcεRI interactions.