An interview with Svar Complement Excellence Award 2026 recipient Professor Christian Karsten, group leader at the Institute of Systemic Inflammation Research at University of Lübeck, Germany.
Professor Christian Karsten remembers clearly the lack of enthusiasm that surrounded the complement system as he ventured into starting his research group. He faced doubts firsthand during his early years, with many clinical colleagues second-guessing research projects focused on the complement system. “They would always ask why I cared about the complement system, reminding me of the field’s stagnated state, and questioning whether there had actually been any progress since the 80s’ teachings.”
The skepticism has now morphed into genuine interest and complement now gets the kind of attention once reserved for T cells and B cells. Prof. Karsten finds himself at the center of this renewed interest, and at the forefront of complement research. In September, he received the Svar Complement Excellence Award 2026, recognizing his dedication and achievements in advancing the understanding on the role of C5a and its two receptors in physiological and disease processes.
The beginning of a new era in complement research traces back to the arrival of novel complement-targeted therapies. The release on the market in 2007 of Eculizumab, a monoclonal antibody targeting the complement anaphylatoxin C5 and approved for use in different rare autoimmune diseases, changed everything. Researchers, clinicians, and industry all started to turn their attention to the complement system.
“When Eculizumab was approved, it sparked a renewed interest in the complement system. People started realizing that complement likely plays a role in many disease states such as autoimmune conditions. Especially since 2020-2021 we are seeing an explosion of complement-targeting therapeutics coming to the market.” explains Prof. Karsten.
“Now I give lectures on complement to both clinicians and industry, as they are eager to know how to leverage the complement system for therapeutic development. And we see more clinical trials with complement therapeutics being initiated. This is all very encouraging and exciting.”
Unlocking the role of C5a’s receptors
Prof. Karsten'a His team's research centers on the anaphylatoxin C5a and its receptor C5aR1 and C5aR2. For years he has focused on the role of C5a/C5a receptors axes in autoimmune bullous dermatoses (AIBD), with particular attention to epidermolysis bullosa acquisita, a severe autoimmune disease of the skin. His team showed that C5aR1 plays an essential role in disease progression, specifically by recruiting neutrophils that cause skin damage.
To track the expression of C5aR1 directly rather than relying on antibody staining, the team, at that time still under Prof. Jörg Köhl, engineered a GFP reporter floxed mouse model, where the expression of C5aR1 can be “switched off” in specific cell types.
“The reporter mouse became an invaluable resource to track expression without relying on existing antibodies,” he recalls. “So, we asked: ‘Why stop there?’ While C5aR1 is well described in literature, very little is known about C5aR2. We therefore decided to build a second floxed tdTomato mouse line for C5aR2, so that we could study the effects of C5aR2 expression.”
Identifying the role of C5aR2 in pregnancy and metastatic tumors
With this powerful tool in his hands, Prof. Karsten was finally able to widen the scope of his investigation into C5a receptors. As he focused on better understanding the expression and functions of C5aR1 and C5aR2, it was becoming clearer that the effects of these two receptors are not limited to immune regulation, with more evidence emerging of their role in tissue growth.
Prof. Karsten’s team identified that C5aR1 and C5aR2 were co-expressed in most cell types. But it was the exceptions that caught their attention. In these mouse models, naïve B cells and NK cells expressed only C5aR2. Looking particularly into NK cells, the researchers found that the expression of C5aR2 regulated IFN-γ production.
Inspired by his research studies during his PhD on reproductive immunology, he turned his attention to the well-established link between pregnancy and IFN-γ levels. Uterine natural killer (uNK) cells are known to be important for placental angiogenesis and development during the first trimester of pregnancy, contributing to the remodeling of the spiral arteries and helping the trophoblast to attach to maternal tissue.
By modulating the expression of C5aR2 receptor in uNK cells, he observed that mice deficient in C5aR2 had lower breeding efficiency than their C5aR2-proficient counterparts, and showed higher levels of IFN-γ. The findings were a reminder of the fine range of IFN-γ levels the cells need to maintain, since too low levels cause a thickening of arteries, while too high levels dilate them excessively.
That’s where Prof. Karsten also draws striking comparisons between his C5aR2-deficient mouse models and parasitology. It appears that the morphology of C5aR2-deficient mice’s uterus resembles that of mice infected with Toxoplasma gondii, a parasite known to cause pregnancy complications. That overlap has motivated him to further investigate C5aR2’s influence on immune-cell infiltration into the uterus, especially its mechanism of action in NK cells during pregnancy.
“Once we established the connection between C5aR2 and NK, looking into tumor growth felt like a natural transition. In fact, just like in pregnancy, tumors also need to promote tissue growth to create new blood vessels, and there as well we see an important role played by NK cells,” Prof. Karsten explains.
His team initiated a project on metastatic tumors investigating C5aR2’s regulation of metastasis in mouse models. “While NK cells are not particularly involved in controlling solid tumors, they are very potent in controlling metastatic cells,” he continues.
By injecting melanoma cells via the tail vein, the team observed that the lungs of C5aR2-deficient mice are better protected from metastatic cells, with far fewer nodules than in wild-type mice. They believe this response relates – at least in part – to the observed three- to five-fold increase in NKp46 receptors seen in C5aR2-deficient NK cells, suggesting a potential link between C5aR2 and metastatic growth.
This collection of evidence shows that there’s still so much to be discovered about the functions of C5a and its receptors in particular, and of complement in general. The more we look into complement proteins’ functions, the more we see that they potentially perform different roles and responsibilities in different context both in physiological and disease states.
What's Next for Prof. Karsten's Research
Prof. Karsten’s future projects aim at deciphering how C5aR2 functions in different cell types and contexts. On the one hand, he plans to investigate the role of C5aR2 when it is co-expressed with C5aR1, and on the other, further describe when and how it acts during pregnancy, tumor progression, and B-cell development.
“In every context where we look and check, we see a role of the anaphylatoxin receptors with distinct roles for C5aR1 and C5aR2. And it's really interesting to observe under which circumstances and when one receptor has a more important or prominent role than the other. Furthermore, it will be important to understand how they regulate each other and act independent of one another.”
For that, he intends to delve deeper into the receptor’s regulatory properties in NK cells, during pregnancy. The evidence of NK cells’ role in fighting metastatic tumors is also of great interests, with much more to be discovered and described.
And how will the Complement Excellence Award help? Prof. Karsten explains that the extra funding will be very helpful in funding experiments that require complex and expensive techniques. In particular, he wants to invest into spatial transcriptomics experiments for in-depth in vitro expression profiling in the uteri of pregnant mice and in tumor-adjacent and tumor-free lung regions.
With the need for securing research funding being an ever-present high-stakes activity in academia, the extra leeway that this award grants to Prof. Karsten can help give more freedom to investigate important but complex leads.
Advice to the next generation of researchers
When asked about any advice he would like to share with future researchers, Prof. Karsten offers general, complement-independent keywords: resilience and conviction.
“If academic research is your thing and something you are truly passionate about, stick to it; don’t give up. In the end, your determination and passion will be rewarded.”
It is thanks to the resilience and determination of scientists like Prof. Karsten who believed that the complement system had and still has much more to give to scientific and medical progress that this field of research is now thriving and becoming one of immunology’s fastest-growing fields.
