University of Chicago researchers have made a groundbreaking discovery in the field of immunology, potentially opening up new avenues for fighting disease. In a recent study, the team identified several small molecule compounds capable of inducing “trained immunity” – a phenomenon where the innate immune system develops an enhanced response to future infections.

A Surprising Discovery

One of the most unexpected findings was that glucocorticoids, a class of steroids traditionally viewed as immunosuppressive, can actually induce trained immunity under certain conditions. This challenges long-held assumptions about these compounds and suggests they may have more complex effects on the immune system than previously thought.

Expanding the Toolbox

Until now, researchers studying trained immunity have relied primarily on complex biological molecules like β-glucan or the BCG vaccine. This new work dramatically expands the arsenal of compounds known to induce this effect, including many well-characterized small molecules with tunable properties.

Dr. Elena Rodriguez, lead author of the study, explained: “By identifying these small molecule inducers, we’ve opened up new possibilities for studying the mechanisms behind trained immunity. This could lead to more targeted and effective ways of harnessing this phenomenon for therapeutic purposes.”

High-Throughput Screening Yields Results

The team used a high-throughput screening approach, testing a library of 2,000 drugs and drug-like compounds for their ability to induce trained immunity. This systematic search yielded over two dozen promising candidates across several chemical classes.

Importantly, many of these compounds induce a training effect without causing initial immune activation – a limitation of some previously known inducers. This property could make them particularly useful for prophylactic applications.

Looking Ahead

The researchers selected seven top candidates for further characterization and in vivo testing. These studies will help establish the real-world potential of these compounds for enhancing immune responses.

Dr. James Chen, a co-author on the study, commented on the future implications: “This work really expands our understanding of trained immunity and its potential applications. We’re excited to explore how these compounds might be used to improve vaccine efficacy or develop new approaches to preventing and treating infectious diseases.”

As research in this field progresses, it’s clear that trained immunity holds significant promise for next-generation therapeutic design. The discovery of these small molecule inducers represents an important step forward, providing new tools for both basic research and potential clinical applications.

The full study, detailing the screening process and characterization of the identified compounds, was published in the journal Proceedings of the National Academy of Sciences.

 

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