Sophie Ugolini: a visionary in immunology

With her research on how the nervous system influences the regulation of immunity, Sophie Ugolini is charting an unprecedented course in immunology. When she turned her attention to it in 2012 after several years of deciphering immune regulation mechanisms, immunology was a new discipline. This bold choice has earned Ugolini two major funding opportunities which, since 2015, have contributed to a motivated team and innovative research.

Sophie Ugolini, Research Director at Inserm and leader of the Neural Regulation of Immunity team at the Marseille-Luminy Immunology Centre (unit 1104 Inserm/Aix-Marseille University/CNRS).

Nestled in the heart of the Calanques National Park, on the campus of Aix-Marseille University, the Marseille-Luminy Immunology Centre can be proud to count Sophie Ugolini among its ranks. A site with which this Inserm Research Director and Neural Regulation of Immunity team leader is very familiar because she trained there and has since used her professional experience to develop the new discipline of neuroimmunology. An emerging field. “When I began working in it in 2012, no one was talking about it. Yet the link between the nervous system and the immune system seemed obvious to me and stoked my curiosity. When infection or injury strikes, the pain perceived by the nervous system is a warning signal for the body, and the immune system is activated simultaneously. My hypothesis was that the systems could “cooperate” to fight pathogens and heal tissues. We decided to run with this intuition and through close collaboration with neurobiologist Aziz Moqrich our unit explored the intimate mechanisms of neuroimmune regulation,” she recalls.

Back then, despite some of her colleagues not supporting her project, which they considered too exploratory, she applied for – and in the end obtained – funding. Major funding. In 2014, she obtained a European Research Council Consolidator grant representing €2 million euros over a five-year period and a turning point for her career. “Support like that means we can do ambitious projects and focus on them without having to constantly pause to find new funding,” she clarifies. Finally, she was able to set up a motivated team to dedicate herself to this innovative theme.

A new discipline

From concept to demonstration, I had a lot to put into place to prove that my intuitions had a relevant scientific basis,” she recalls. She used genetically modified mouse models developed by neurobiologists to analyse how the absence of a subpopulation of sensory neurons impacts immunity. Her work proved to be a resounding success. For example, her unit demonstrated that neurons involved in pain play an antiviral role against the herpes virus HSV‑1, which causes painful blisters. She also proved that a subpopulation of sensory neurons innervating the skin controls inflammation and the repair of cutaneous tissues following exposure to ultraviolet light. What is more, her team highlighted the anti-inflammatory role of the TAFA4 protein produced by the sensory neurons. “A major discovery that could lead to new therapies for controlling inflammatory diseases,” she believes.

Having created a real dynamic in this area, she obtained a €2.3 million Impulscience grant from the Bettencourt-Schueller Foundation to develop an ambitious five-year project. “We will continue our research, focusing particularly on the therapeutic effect of stroking! Our hypothesis is that beyond its social and comforting role, stroking could play a direct role in immunity. We know that the anti-inflammatory molecule TAFA4 is produced by a subpopulation of neurons that are sensitive to light touch. Thanks to new animal models, we will study the possible impact of the stimulation of these neurons on immunity.

The fundamentals remain

But while the originality of neuroimmunology attracted a lot of attention, this was not to obscure Ugolini’s contribution to pure immunology, with around thirty years at the service of this discipline. Intrigued by the mechanisms that regulate immune and inflammatory responses, she set herself the goal of understanding how they eliminate pathogens or cancer cells without altering the other surrounding healthy cells. In particular, she devoted a lot of time to studying natural killer (NK) cells, which target cancer or virus-infected cells. This earned her major publications and participation in a clinical trial based on the infusion of activated NK cells in cancer patients. Significant advances recognised by the Inserm Research Prize in 2012.

‘The journey has been challenging but so exciting,’ she acknowledges. This is all the result of an insatiable curiosity, unwavering fascination in the face of the extraordinary complexity and robustness of living beings, able to defend themselves against aggression, adapt, self-repair... “The more knowledge we acquire, the more this complexity is revealed and opens the door to new questions and new processes that we weren’t suspecting. I’m proud to add a few pieces to this jigsaw that is still very far from completion. I’m also proud of what I do. It’s such a privilege. We’re paid to understand!” However, she believes that curiosity is not enough – a large dose of work, determination and perseverance is also needed. On this subject, she reveals that she has continued her quest for knowledge by exploring the placebo effect: “This effect, which we can describe as therapeutic since it can reduce symptoms despite being based only on the trust placed in a treatment that is actually inactive, has always been of interest to me.” Meaning that she still has a certain number of avenues to explore and that the future of neuroimmunology is looking bright...

Sophie Ugolini is a Research Director at Inserm and leader of the Neural Regulation of Immunity team at the Marseille-Luminy Immunology Centre (unit 1104 Inserm/Aix-Marseille University/CNRS).