At our October Virtual Education Session, Dr Karoline Raven from the Queensland University of Technology joined us to unpack a question that sits right at the centre of scleroderma research: what is actually driving the inflammation behind this condition, and why does the environment around us play such a big part in it.

Karoline is a post-doctoral research fellow at QUT’s Centre for Immunology and Infection Control, working within the experimental rheumatology group. She completed her PhD in immunology at the University of Queensland in 2025, after a Bachelor of Medical Science from the Australian National University and first class honours from the John Curtain School of Medical Science. Her research looks specifically at environmental triggers for inflammation, with systemic sclerosis one of several conditions she’s focused on.

Understanding Autoimmunity: Why the Immune System Turns on Itself

To understand environmental triggers, it helps to understand the immune system itself. Karoline described it in two parts. The innate immune system is the first responder, made up of cells like macrophages that sense and clear threats the moment they appear. The adaptive immune system is the specialised response that follows, built around T-cells and B-cells that learn and target specific threats.

Autoimmunity happens when environmental triggers combine with genetic factors to confuse this system, causing it to misidentify healthy tissue as a foreign threat. Once that happens, the immune response stays switched on, continuing to attack tissue that was never the problem in the first place.

The Environmental Triggers Under the Microscope

Karoline’s broader research portfolio spans systemic sclerosis, ankylosing spondylitis, chronic inflammatory response syndrome, and localised scleroderma or morphea. Across these conditions, her team is studying a wide range of environmental triggers, including mould mycotoxins, temperature, viruses such as Epstein-Barr, diet, carcinogens, and silica exposure near mining sites.

The goal behind all of this is to uncover new mechanistic insights, improve diagnostics, and identify therapeutic options, including immediate lifestyle changes and the repurposing of existing drugs. Systemic sclerosis itself is a rare rheumatic autoimmune disease that affects multiple body systems, causing progressive fibrosis across the skin and internal organs. Inflammation always comes before fibrosis, yet current treatments predominantly target the fibrosis rather than the inflammatory triggers that caused it. That gap is exactly where Karoline’s research is aimed.

Temperature, Raynaud’s and the Missing Piece of the Puzzle

A large part of the session focused on temperature, and for good reason. Many people with systemic sclerosis experience Raynaud’s phenomenon, where small blood vessels spasm and narrow, reducing blood flow and causing pain, colour change, numbness and disability. It’s typically triggered by cold temperatures and stress.

What struck many attendees was Karoline’s point about where the research has and hasn’t gone. The vessel spasming itself is well documented, but the underlying inflammatory processes that cause Raynaud’s in the first place have been largely uninvestigated. That’s a meaningful gap, because it means treatment has mostly focused on managing the symptom rather than understanding what’s driving it.

Climate change is adding another layer to this. In Australia, a heat wave is defined as three consecutive days of unusually high maximum and minimum temperatures, while a cold wave is a rapid fall in temperature within 24 hours that persists for multiple days. Both are becoming more frequent, with sharper temperature shifts. Karoline explained that during these events, internal body temperature can become dysregulated by up to two degrees Celsius, which drives inflammation in a similar way to a fever response. As these weather patterns increase, so does the likely impact on both quality of life and the healthcare system.

What’s Happening at a Cellular Level

Macrophages, which Karoline nicknamed “Pac-Man cells”, play a central role in both heat and cold responses. Alongside heat shock proteins, they signal pattern recognition receptors to release inflammatory cytokines and present antigens to T-cells, effectively setting off the inflammatory cascade.

In people with systemic sclerosis, specific heat shock proteins (47, 70 and 90) are upregulated, generating self-harming autoantibodies that drive chronic systemic inflammation and fibrosis. This is the mechanism Karoline’s current study is built around. The first aim is to determine how sustained temperature variation affects the activation of immune cells in people with systemic sclerosis, using patient-donated blood cells exposed to controlled temperatures between 35 and 39 degrees Celsius, analysed through flow cytometry, qPCR and Western blot.

The second aim takes this further using organ-on-a-chip technology, sometimes called skin-on-a-chip. These microfluidic devices recreate artificial skin using an epithelial barrier, a fibroblast layer and an endothelial blood vessel layer, allowing the team to track immune cell recruitment and cytokine production using fluorescent tags and live microscopy. The long-term goal is to build an artificial patient on a chip, which could dramatically speed up drug testing and repurposing, well ahead of testing in mice.

The Gut Microbiome and Diet

Karoline also shared details of a five-year gut microbiome project, designed to understand baseline bacteria, metabolites, immune responses and dietary triggers in systemic sclerosis over a 12-month period, with the aim of better predicting inflammatory flares. The project includes collaborating with a dietician to develop a targeted, disease-specific diet and clinical guidelines, and investigating whether a licensed prebiotic called 2-FL, currently trialled for Crohn’s disease and ulcerative colitis, could be repurposed to help regulate the gut microbiome in systemic sclerosis. Rather than stimulating the immune system, 2-FL works by rectifying and stabilising the gut microbiome, which makes it a genuinely promising, low-risk option worth watching.

On the diet question more broadly, Karoline noted that the autoimmune protocol diet has been shown to reduce inflammation, while a Mediterranean style diet may better shift the gut microbiome, based on limited but encouraging inflammatory bowel disease research. She was candid about a frustration many in the scleroderma community will relate to: medicine often treats the body in silos, with specialists focused on individual systems rather than the whole person. She’d like to see more multidisciplinary clinics that bring researchers, dieticians, nurses and specialists together around the same table.

Silica Exposure and Occupational Risk

One of the more eye-opening parts of the session covered silica. Karoline’s team is investigating how silica exposure drives systemic sclerosis, using epidemiological data, patient blood cells and airway-on-a-chip models that represent the nose, upper airway and lower airway (lung).

Crystalline silica particles, common in construction, mining and stone benchtop work, are engulfed by lung macrophages, which can trigger an overactive immune response capable of transitioning into autoimmune disease over time. Importantly, Karoline pointed out that standard surgical masks aren’t enough to block these extremely small particles. Full respirators are needed, and wider adoption of proper protective equipment across affected industries has historically lagged behind the risk.

Fatigue, Spoon Theory and Why Rest Matters

Karoline spoke about the importance of rest for anyone living with an immune disorder, using the well-known “spoon theory” to explain how routine tasks can consume far more energy than they appear to from the outside. Overexertion isn’t just tiring. It can genuinely trigger inflammatory flares, which makes pacing and rest a real part of managing the condition, not a luxury or an afterthought.

Living with an Invisible Illness

The session also touched on the particular challenge of living with an invisible illness, and the misperceptions that can come with it around age and physical appearance. If this is something you navigate often, or something your family and friends are still learning to understand, Scleroderma Australia has recently released a resource on our website called “Supporting Someone with Scleroderma“, designed to help the people around you understand the condition a little better.

How You Can Help the Research

Research like this relies on participation, and healthy controls are just as valuable as patient volunteers. Karoline explained that recruiting family, friends and support networks as healthy controls helps researchers understand why some people in the same household develop the disease while others don’t. Participation is kept simple and dignified wherever possible, including at-home toilet paper swab kits for gut microbiome samples that remain stable at room temperature, so there’s no need for a clinic visit just to take part.

Frequently Asked Questions

1. What causes inflammation in scleroderma? 

A combination of genetic factors and environmental triggers, including temperature, viruses, diet, mould and silica exposure, can cause the immune system to misidentify healthy tissue as a threat, keeping inflammation active.

2. Why does temperature affect scleroderma symptoms? 

Heat shock proteins and macrophages respond to both heat and cold by releasing inflammatory cytokines. In systemic sclerosis, this process is amplified, and internal body temperature can fluctuate during extreme weather in a way that drives inflammation similar to a fever response.

3. What is being done to understand Raynaud’s phenomenon better? 

While the vessel spasming in Raynaud’s is well documented, the underlying inflammatory processes causing it have been largely unstudied. Current research is working to close that gap using patient blood cells and organ-on-a-chip technology.

4. Can diet make a difference to inflammation? 

Early research suggests the autoimmune protocol diet can reduce inflammation, and a Mediterranean-style diet may help shift the gut microbiome. A five-year study is now underway to better understand dietary triggers and develop disease-specific guidelines.

5. How can I get involved in scleroderma research? 

Many studies recruit family and friends as healthy controls alongside people living with scleroderma. Participation often involves simple, at-home collection methods, so it’s worth asking your care team or state association what’s currently open.

TL;DR

At our October Virtual Education Session, Dr Karoline Raven from QUT shared how environmental triggers, including temperature, silica, viruses and diet, interact with genetic factors to drive inflammation in systemic sclerosis. Her research is working to understand what happens at a cellular level during temperature change, how the gut microbiome influences flares, and how occupational exposures like silica may contribute to disease onset. The key message: inflammation comes before fibrosis, and understanding what triggers it is central to better treatment in the future.

Conclusion

Understanding what triggers inflammation in scleroderma is one of the clearest paths toward better treatment down the track. From temperature and the gut microbiome to occupational exposures like silica, this research is steadily closing the gap between what the scleroderma community has long known from lived experience and what the science can now explain.

For those living with scleroderma, staying informed and connected can make a world of difference. Find out more about support in your area by clicking here.

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These sessions provide an opportunity to engage with medical professionals and allied health experts who will address common questions about scleroderma and related topics.