How monocyte-derived macrophages and microglia shape the inflammatory environment of the brain

What have your Ph.D. studies focused on?

"My thesis demonstrates how peripheral monocytes, and central microglia contribute to neuroinflammatory processes across the human lifespan and in distinct pathological contexts. Monocytes are a type of white blood cell that circulate in the bloodstream and have the ability to migrate into tissues, where they can differentiate into macrophages. In contrast, microglia serve as the specialized immune cells that reside within the central nervous system (CNS). Through the integration of high-resolution immunophenotyping, transcriptional profiling, and patient-derived induced pluripotent stem cell (iPSC) models, the research I conducted during my time as a doctoral student underscores the remarkable adaptability and plasticity of innate immune cells in aging, stroke, and Gaucher Disease (GD).

The first paper in my thesis demonstrated that aging induces transcriptional changes in monocyte subsets in a sex-specific and subtype-dependent manner, with prominent alterations in the expression of neuroinflammatory and regenerative genes. These findings not only provide a nuanced view of immune aging but also establish a cellular framework for understanding sex-linked vulnerabilities to neuroinflammatory disease. The second paper, extended this investigation into dynamic immune responses following ischemic stroke, showing that monocyte subset fluctuations and gene expression profiles are temporally regulated and predictive of neurological recovery. The identification of early post-stroke immune signatures linked to long-term outcomes offers new possibilities for prognostication and immune modulation in stroke rehabilitation. The third paper introduces a patient-specific iPSC-derived microglial model for neuronopathic GD, revealing disease-associated deficits in inflammatory signaling and lysosomal function. This platform paves the way for personalized interrogation of microglial dysfunction and the development of targeted therapies.

A unifying theme across these studies is the immunological plasticity shared by monocytes and microglia: cells that, while distinct in origin and niche, exhibit remarkable adaptability in response to environmental cues. This plasticity, however, is not uniformly beneficial; it can support repair or perpetuate dysfunction depending on the context. These findings underscore the limitations of binary activation models and highlight the need for high-resolution, subset-specific characterization of innate immune responses. By embracing this complexity, future research can better delineate the conditions under which immune plasticity promotes resilience versus pathology, paving the way for more precise and personalized immunomodulatory strategies.

Collectively, the studies of my thesis highlight the central role of monocyte and microglia dynamics in regulating the balance between injury and repair in the brain. These findings highlight the critical need for a lifespan-spanning, immune-focused approach to understanding neuroinflammation that considers cellular heterogeneity, sex-specific regulation, and disease context. They also demonstrate how immune cells not only reflect but also actively shape the trajectory of neurological health and disease, offering critical insight into potential biomarkers and therapeutic targets."

Can you tell us more about the cover of your thesis?

"The cover of my thesis, “Neuroinflammatory Tides: Between Stellar Rupture and Coral Renewal”, reflects both the scientific themes and my personal inspirations—space and the ocean, two realms I've always been deeply fascinated by. It features a human face split by a waterline, symbolizing the asymmetry one must be aware of in the context of stroke. Above, a night sky symbolizes stroke, with constellations representing neuronal connections, red stars stroke, and monocytes as planets. The red tones evoke the pro-inflammatory potential of macrophages, where beauty in space often arises from destruction. Below the surface, the ramified coral structures represent microglia and swollen Gaucher cells. The green colours reflect anti-inflammatory and regenerative processes, as in the underwater world, light is where there is life and healing, mirroring the restorative potential of immune cells in the brain. The upper face has masculine features, while the submerged face is more feminine, highlighting the biological sex differences explored in my research. The cover is a visual metaphor for the duality of inflammation: destruction and repair, chaos and renewal."

How did you end up doing a Ph.D. at Lund University and the Lund Stem Cell Center?

"Curiosity has always been a driving force in my life, which was nurtured over the years, from dry ice experiments at birthday parties to tide pool explorations and building inventions with my grandfather. As I grew older, science became my way of understanding the world. I studied biochemistry for its structure and logic, but found myself increasingly drawn to the mysteries of the brain, especially how simple molecular mechanisms scale up to something as profound as thought or emotion. Neuroscience felt like the perfect blend of complexity and wonder.

Lund University and the Lund Stem Cell Center offered the ideal environment to explore these questions. The interdisciplinary nature of the research, the opportunity to work with stem cells and immune cells, and the translational focus bridging lab and clinic made it a natural fit."

What have you found the most enjoyable during your Ph.D. studies?

"I’ve especially enjoyed the hands-on experimental work and the process of establishing new techniques, such as generating iPSC-derived monocytes and microglia. Collaborating with other researchers, mentoring students, and presenting at conferences have also been incredibly rewarding. These experiences have not only deepened my scientific understanding but also helped me grow professionally and personally. Seeing the impact of my work and engaging with the broader scientific community has been a true highlight. One of the most fulfilling aspects has also been the opportunity to take full ownership of my research. As first author on several projects, I was responsible for nearly every step: from experimental design and data collection to analysis and manuscript writing. While this level of responsibility was challenging, it also meant I knew every detail of the work, which made the process incredibly rewarding."

What has been the most challenging aspect?

"One of the biggest challenges during my Ph.D. was learning to stand on my own feet as a scientist. From early on, I had to take initiative: designing experiments, troubleshooting protocols, and driving projects forward, often in unknown territory. Working across neuroscience, immunology, and stem cell biology meant constantly learning and adapting.

The pandemic made things even harder. Sample collection was paused, collaborations slowed down, and many opportunities to connect with others simply disappeared. But in that isolation, I found resilience. I learned to navigate uncertainty, set up new methods from scratch, and reached out for expertise when needed. It wasn’t always easy, but it taught me how to be resourceful, persistent, and independent: skills I’ll carry with me far beyond the Ph.D."

What are your plans following your Ph.D. defense?

"Following my defense, I plan to continue working in the field of neuroimmunology, ideally in a translational research setting. I’m particularly interested in postdoctoral opportunities that allow me to further explore immune mechanisms in neurological diseases and contribute to developing therapeutic strategies."

Any tips or advice for future Ph.D. students?

"Stay curious and proactive. Never stop exploring new ideas or fields, even those outside your comfort zone. Build a strong support network, because mentorship and collaboration can make all the difference. Balance is key: taking care of your well-being is essential for sustaining focus and creativity over the long haul. And most importantly, celebrate your progress. Every step forward, no matter how small, is a milestone worth acknowledging," concludes Juliane.