Opportunity is a master of disguise
Autoimmune diseases arise when the body’s defence system, which is designed to protect against infections, mistakenly turns against its own tissues. Instead of distinguishing clearly between harmful invaders and healthy cells, the immune system begins to attack organs and tissues as though they were foreign. This inappropriate response leads to chronic inflammation, a sustained invasion of immune cells into tissues which progressively damages organs and disrupts their normal function.
A wide range of conditions fall under the category of autoimmune disease, each affecting different parts of the body. For example, multiple sclerosis involves damage to the brain and spinal cord, type 1 diabetes affects insulin-producing cells in the pancreas, and Sjögren’s syndrome targets glands responsible for producing saliva and tears. Despite these differences, a central question remains unresolved: why does the immune system attack specific organs in certain individuals?
Although the precise triggers are not fully understood, several important clues have emerged. Autoimmune diseases frequently run in families, suggesting a genetic predisposition. In addition, it is not uncommon for a single individual to develop more than one autoimmune condition, pointing to shared biological mechanisms across diseases. Large-scale genetic studies have reinforced this view, revealing substantial overlap in the genes that increase susceptibility to different autoimmune disorders. Furthermore, the observation that some medications can be successfully repurposed across multiple autoimmune diseases suggests that these conditions may share common underlying pathways rather than being entirely distinct entities.
One emerging and unexpected contributor to these shared pathways is the platelet. Platelets are small, circulating blood cells best known for their role in stopping bleeding and maintaining the integrity of blood vessels. However, research over the past decade has revealed that platelets play a much broader role in the body, including active participation in immune responses. Rather than acting solely as passive responders to injury, platelets can communicate with immune cells and influence their behaviour. Under certain conditions, they may even contribute to the triggering of immune cells that mistakenly target the body’s own tissues. Our laboratory has been at the forefront of uncovering the role of platelets in autoimmune disease. Using well-established experimental models, we have demonstrated that platelet activity is not merely a secondary consequence of inflammation, but rather an early and potentially driving force in disease development.
In a mouse model of multiple sclerosis, we observed that platelets begin to accumulate in the bloodstream at very early stages, before classical signs of disease are evident. These platelets subsequently infiltrate brain tissue, where they are associated with the development of a highly inflammatory environment. Strikingly, platelets were found to directly interact with nerve cells, contributing to their damage and eventual death. Importantly, these events occurred prior to the detection of self-reactive immune cells, which are traditionally considered the primary drivers of autoimmune disease. This suggests that platelet activity may precede and even initiate the autoimmune response. Consistent with this idea, interventions that block platelet activity were more effective at slowing disease progression than some existing therapies used to treat multiple sclerosis.
We extended these findings to a model of type 1 diabetes, in which the immune system targets insulin-producing cells in the pancreas. In this context, we found that platelets specifically localise to structures known as pancreatic islets, which house these insulin-producing cells. Platelet involvement was detected in young animals, well before clinical signs of diabetes, such as elevated blood sugar levels, became apparent. This early platelet activity was associated with disruptions in the normal organisation of islet cells and a marked reduction in insulin production. These findings indicate that platelet-driven damage begins long before the disease is clinically diagnosed, highlighting their potential role as early initiators of pathology.
Further supporting a broader role for platelets in autoimmunity, our studies in a model of Sjögren’s syndrome revealed that platelets infiltrate the salivary glands—the primary targets of this condition. Their presence correlated with inflammation and tissue dysfunction, reinforcing the idea that platelet involvement is not limited to a single disease but may represent a common feature across multiple autoimmune disorders.
Despite this growing body of evidence linking platelets to inflammation and tissue damage, their overall contribution to autoimmunity remains incompletely understood. As a result, therapeutic strategies that specifically target platelets in autoimmune disease have received relatively little attention. Most current treatments focus on suppressing more mature components of the autoimmune process. While these approaches can reduce inflammation and slow disease progression, they do not typically address the earlier stages of the disease process. As a result, patients are often treated only after substantial and sometimes irreversible tissue injury has already occurred.
Our research seeks to address this gap by establishing platelet-targeting as a viable and effective therapeutic strategy for autoimmune diseases. The overarching goal is to identify and characterise the mechanisms by which platelets contribute to disease onset and progression, and to use this knowledge to develop novel treatments that halt disease before irreversible damage occurs. This positioning at the very start of the disease cascade makes platelets an especially attractive therapeutic target. Intervening at this stage could prevent the sequence of events that ultimately leads to chronic inflammation and organ damage, rather than attempting to control it after it is fully established. Another important advantage of targeting platelets is that they have the potential to address shared upstream mechanisms common to many autoimmune conditions. This raises the possibility of developing more universal therapeutic strategies that are both more efficient and more widely applicable.
Furthermore, the relative lack of research in this area means that platelet-targeting remains a largely untapped opportunity for innovation. While other aspects of the immune system have been extensively studied and therapeutically exploited, platelets have only recently emerged as key regulators of immune behaviour. Consequently, there is significant potential to discover entirely new classes of drugs that act through mechanisms distinct from existing therapies. Importantly, our own work demonstrates that inhibiting platelet activity can be more effective than current standard treatments in experimental models, further supporting the idea that this approach could offer meaningful clinical benefits.
Ultimately, our work aims to redefine how autoimmune diseases are understood and treated. By elucidating the central role of platelets in orchestrating immune dysfunction, we hope to lay the groundwork for new diagnostic tools that detect disease at its earliest stages, as well as first-in-class therapies that specifically target platelet-driven mechanisms. Such approaches have the potential to intercept autoimmune disease before significant tissue damage occurs.
In the long term, targeting platelets could represent a paradigm shift in autoimmune therapy, from managing symptoms after the fact to preventing disease progression at its source.