Málstofa Lífvísindaseturs - Mast cells: linking immune sensing to host-protective behavior

Málstofa Lífvísindaseturs föstudaginn 23. janúar kl. 11:00-12:00 í Árnagarði, stofu 301

Fyrirlesari: Dr Thomas Plum, Senior Researcher at the German Cancer Research Center, Heidelberg, Germany.

Title: Mast cells - linking immune sensing to host-protective behavior

Abstract: Mast cells are hematopoietic sensory cells strategically positioned at barrier tissues, often in close proximity to neurons. While notoriously known for their role in the pathology of allergic disease—driving symptoms such as itch, cough, and diarrhea—their evolutionary benefit has long remained elusive. By combining comprehensive immunological analysis with functional behavioral assays, we demonstrate that mast cells serve as a unique immune lineage that functions as a critical bridge between the immune and nervous systems to drive host-protective behaviors.

First, we explore the role of mast cells in antigen avoidance. Using mast cell-deficient mice and models of type 2 immunity, we show that mast cells sensitized with antigen-specific IgE act as "early warning" sensors in the gastrointestinal tract. Upon antigen ingestion, mast cell activation signals an immediate cessation of intake. This avoidance behavior effectively prevents continuous immune activation and protects the host from chronic immunopathology and gastrointestinal inflammation.

Second, we examine the regulatory role of mast cells in modulating itch and skin integrity. Contrary to the traditional view of mast cells solely as itch-inducers, we find that mast cell-derived tryptase, can suppress excessive scratching. In the absence of mast cells, itch responses to certain secretagogues are exacerbated, leading to increased skin barrier damage. We propose that mast cells modulate sensory neurons to lower mechanical pain thresholds, thereby limiting self-inflicted injury from scratching and preserving tissue integrity.

Together, these findings suggest that mast cells, acting in concert with neurons, are versatile immune sentinels. By translating environmental and tissue-derived signals into adaptive behavioral responses—from avoidance to itch regulation—mast cells function as a cornerstone of the behavioral immune system, protecting the organism against both exogenous antigens and exacerbating endogenous signals.

Biography: I was born and raised close to Cologne in Germany. I did my undergraduate studies in Biology at the University of Applied Sciences in Bonn, followed by graduate studies at the University of Freiburg. During my graduate studies, I developed a strong interest for immunology, which led me to study T cell biology with Prof. Chenqi Xu at the Shanghai Institute of Cell Biology and Biochemistry as well as with Wolfgang Schamel at the BIOSS institute of signaling studies in Freiburg. I then had the unique opportunity to join the lab of Prof. Hans-Reimer Rodewald at the German Cancer Research Center in Heidelberg. This also led me to change fields and study mast cells, an enigmatic cell type with unclear beneficial functions. During my doctoral studies I conducted a proteomic “inventory” of mast cells, the results of which suggested that yet undiscovered mast cell functions may lie within neuro-immune interactions. Shortly before we published the proteome paper I conducted the first experiment showing that mast cells promote avoidance. Because of the major implications of this discovery, I chose to continue my postdoctoral studies in the Rodewald laboratory and dissect he molecular mechanism of antigen-avoidance, which we gladly published last year. For my future research, I plan to build upon these findings and explore fundamental questions in mast cell biology and neuroimmune interactions.