Project Details
Projekt
Elucidating the roles of the NLRPlO inflammasome in regulating malignancy and autoimmunity
Applicants
Professor Dr. Eran Elinav; Professor Dr. Eicke Latz
Subject Area
Clinical Immunology and Allergology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 569256642
Inflammasomes are critical and highly conserved cytoplasmic innate immune sensors of cellular and exogenous stress. Upon activation, they orchestrate Caspase-1-dependent IL-1β and IL-18 secretion and trigger protective cell death, playing a central role in preventing tissue damage and infection. Over the past decade, the Latz and Elinav groups have significantly contributed to unraveling the impact of inflammasomes on human health, including the discovery of three of the seven known inflammasomes, AIM2, NLRP6 and NLRP10, resulting in joint major discoveries (joint back-to-back Nature Immunology, 2023). Despite these advances, most inflammasome research, particularly on NLRP10, has focused on their roles in innate immune cells such as macrophages and dendritic cells, while their functions in epithelial and adaptive immune cells remain largely unexplored. We propose to expand inflammasome research by mechanistically elucidating the role of our jointly discovered NLRP10 inflammasome in epithelial cells, B cells, and related malignant and autoimmune diseases. Preliminary results from our groups indicate cancer-specific upregulation of NLRP10 in bladder epithelial cells and a marked loss of B cells in NLRP10-deficient mice. Accordingly, this collaborative project aims to dissect NLRP10 inflammasome activation, formation, and function in (1) the urothelium during bladder cancer and (2) B cells in systemic lupus erythematosus (SLE). We plan to jointly address these two objectives by utilizing various unique genomic, cellular and chemical tools developed by the two labs as part of our extensive ongoing collaboration. This includes genetic manipulation of NLRP10 in mice and patient-derived cells to establish its role in health and disease, single-cell transcriptomics to decode its gene regulatory functions in bladder cancer and SLE, metagenomic sequencing and germ-free mouse models to assess microbiome-mediated NLRP10 activation, and advanced techniques such as flow cytometry, multiplex ELISA, mass spectrometry, and BCR sequencing to uncover the molecular mechanisms linking NLRP10 to carcinogenesis and autoimmunity. In a joint strategic effort from both groups, we share insights, results, and biological and molecular reagents from in vivo, ex vivo and in vitro experiments. This work will provide novel perspectives on the function of the NLRP10 inflammasome in epithelial cells and adaptive immune cells in malignancy and autoimmunity. Beyond expanding fundamental immunology, our findings will hold important translational value and further reinforce a globally recognized collaboration between two leading researchers in complementary fields while advancing bold and previously unexplored areas of inflammasome biology.
DFG Programme
DIP Programme
International Connection
Israel
