Lipid droplets serve as a control hub for immune defense
Lipid droplets within skin cells act as a control hub for immune defense: the important immune receptor NLRP10 is activated at these tiny intracellular fat droplets in response to cellular stress. Researchers at the University of Hohenheim in Stuttgart and the University of Bonn have uncovered this previously unknown mechanism of immune defense. Their findings improve our understanding of inflammatory skin diseases such as atopic dermatitis and could ultimately contribute to the development of new therapeutic approaches. The study has now been published in the journal EMBO Reports.
The skin forms the body's first line of defense against pathogens and environmental stressors. To detect damage and cellular stress, skin cells are equipped with specialized sensors of the innate immune system. One such sensor is the protein NLRP10, which has been studied for more than a decade by the research group led by Professor Thomas Kufer at the Institute of Immunology, University of Hohenheim.
Previous work by the team had already shown that NLRP10 functions as a stress sensor in keratinocytes - the predominant cell type of the epidermis - and is capable of triggering immune responses. Until now, however, it remained unclear how and where within the cell this receptor becomes activated.
Lipid droplets play an active role in immune defense
The newly published study now provides the answer. In collaboration with the structural biology group of Professor Matthias Geyer at the University of Bonn, the Hohenheim researchers demonstrated that NLRP10 accumulates at lipid droplets when cells experience stress. These intracellular fat droplets are best known for storing energy, but they also appear to play an important role in regulating immune processes.
"We were able to show that NLRP10 specifically localizes to lipid droplets, where it assembles into larger protein complexes - a crucial step for its activation," explains first author Dr. Timo-Daniel Voß, a postdoctoral researcher at the University of Hohenheim. "To our knowledge, this mechanism has not previously been described for any other comparable immune receptor."
For the study, the researchers combined a range of cellular and molecular biology techniques. They induced cellular stress in human epithelial cells and keratinocytes and used fluorescently labeled protein variants together with advanced microscopy to track the behaviour of NLRP10 within the cell.
By introducing targeted modifications into specific regions of the protein and comparing different NLRP10 variants, the team demonstrated that an evolutionarily conserved region at the protein's C-terminus controls both its recruitment to lipid droplets and the formation of larger protein complexes - a key step in receptor activation.
New opportunities for skin disease research
The findings provide important insights into how immune responses are regulated in the skin. NLRP10 has long been associated with inflammatory skin disorders, including atopic dermatitis.
"By identifying the site where NLRP10 is activated, we now have a much clearer understanding of how this receptor functions," says immunologist Professor Thomas Kufer. "These findings open up new opportunities to identify the signals that activate NLRP10. In the long term, this could help pave the way for new therapeutic strategies to treat inflammatory skin diseases."
The study also highlights the growing importance of lipid droplets in immunology research. Once regarded primarily as cellular fat storage organelles, they are increasingly recognized as key regulators of immune and inflammatory processes.
Publication
Voß, T. et al. (2026): C-terminal lysine residues localise NLRP10 at lipid compartments and govern NLRP10 oligomer formation. EMBO Reports. DOI: https://doi.org/10.1038/s44319-026-00839-9
Background: Human cell cultures instead of animal experiments
No animal experiments were performed for this study, and no animal-derived cells were used. Instead, the researchers primarily worked with HeLa cells, a human cell line established in 1951 from tumor tissue donated by the American patient Henrietta Lacks. HeLa cells were the first human cell line capable of indefinite growth in culture and remain among the most widely used cell lines worldwide, playing a central role in immunology, cancer research, and vaccine development.
The original HeLa cells were obtained without the knowledge or consent of Henrietta Lacks or her family - a practice that would be considered unethical by today's standards. Her case became a landmark in the development of ethical guidelines for biomedical research. Today, the legacy of Henrietta Lacks is honored by a dedicated foundation.
The University of Bonn and the University Hohenheim are committed to transparency regarding the use of animals in research. It explicitly indicates when scientific studies - as in this case - have been conducted without animal experiments and provides information whenever animal research is involved. Both the University of Hohenheim and the University of Bonn are among the first signatories of Germany's nationwide Transparent Animal Research Initiative, launched in 2021.
Further information is available at:
https://www.uni-bonn.de/tierversuche & www.uni-hohenheim.de/tierversuche
Contact
Professor Dr. Thomas Kufer
Institute of Immunology
University of Hohenheim
Phone: +49 711 459 24850
Email: thomas.kufer@uni-hohenheim.de
Prof. Dr. Matthias Geyer
Institute of Structural Biology
ImmunoSensation3 Cluster of Excellence
University Hospital Bonn and University of Bonn
Tel. +49 228 287-51400
E-Mail: matthias.geyer@uni-bonn.de
