Photograph by Erwin Wagner
How does inflammation spread through the body? Chronic systemic inflammation (CSI) is associated with the progression of different diseases, including psoriasis, atopic dermatitis and cancer. Researchers in the ERC-funded CSI-FUN project are investigating the underlying molecular mechanisms behind CSI and how it spreads through the body, as explained by Erwin Wagner, the principal investigator of the study. An inflammatory response may originate in a given organ like the skin, but it can then spread more widely and affect the entire body, causing serious health problems. Based at the Medical University of Vienna (MUV), Erwin Wagner and his group are investigating the underlying mechanisms behind CSI. “We are trying to find the mechanisms by which the original signal – which elicits the inflammatory response – spreads through the body in a systemic way,” he outlines. This research relies to some extent on mouse models for two common inflammatory skin diseases – psoriasis and atopic dermatitis – in which CSI plays a major role in progression. “We aim to describe how inflammation from the skin spreads through the body and affects different sites and organs,” says Erwin Wagner. “Around a third of psoriatic patients develop psoriatic arthritis, a form of joint disease, which often emerges many years after patients are diagnosed with psoriasis.”
is the communication between the tumour and the whole organism. “We’re looking at the cross-talk, the communication that takes place between a tumour and the organism. We’re investigating what happens when the tumour sends out signals to start inflammation,” he says. “In each of these cases we’re looking systemically. For instance, in cachexia we look across the different organs in the body, keeping an open mind about what we might find.” Researchers in the Wagner group ultimately aim to identify the factors behind the initiation of CSI, which then kicks off a cascade leading
to the progression of disease. One important event in the development of CSI is the release of inflammatory mediators, including inflammatory cytokines like IL-6 and IL-17, which activate pro-inflammatory signalling pathways. “These cytokines are important therapeutic targets for both skin diseases and CAC,” outlines Wagner. In his research, Wagner is using mouse models to investigate the molecular mechanisms behind CSI, while he also has access to samples from human patients. “My lab is well-known for generating innovative mouse models of human diseases,
Visualisation of collagen packing density in a mouse knee section using picrosirius red staining and polarized light.
Deciphering organ cross-talk The aim of the study is to build a broader picture of the communication between the skin and the joints, and to identify which molecules, signalling pathways and cells are involved. Researchers in this project are also looking at CSI in the context of cancer associated cachexia (CAC), a metabolic syndrome which can develop in the late stages of cancer and is associated with weight loss. “Many tumours are highly inflamed, and this inflammation can then spread throughout the body, leading to weight loss,” explains Wagner. Rather than looking at the actual tumour itself, the focus of the Wagner group
www.euresearcher.com
17