A11 | NLRP10 inflammasome mediated anti-inflammatory cell death
Prof. Dr. med. Eicke Latz
Institute of Innate Immunity
University Hospital Bonn, University of Bonn
Contact: eicke.latz(at)uni-bonn(dot)de
For more information visit: Latz Lab
Abstract
This project is funded within the 2nd funding period of the SFB 1403, starting from 2024
The laboratory focuses on identifying the most proximal mechanisms of innate immune activation involved in mediating autoinflammatory and chronic inflammatory diseases. The lab employs systems immunology, unbiased experimental biology and human trials to decipher how the innate immune system maintains immune homeostasis or contributes to the pathogenesis of inflammatory diseases.
The uncovered mechanisms of innate immune activation can be relevant to a range of auto-inflammatory, auto-immune and chronic inflammatory diseases. Thus, their disease relevance is typically tested using a range of preclinical models and human translational studies with biomaterial from patients and observational clinical trials. The lab has identified novel therapeutic targets and spun-out several biotech companies to translate the basic research findings into novel medicines and preventative approaches.
Recent Publications
2026
Duewell P, Diefenbach A, Latz E. Immune dyshomeostasis in lifestyle-associated diseases: a new paradigm for personalized medicine and prevention. Curr Opin Immunol. 2026 Mar 16;100:102754. doi: 10.1016/j.coi.2026.102754. Epub ahead of print. PMID: 41844070.
Merbecks AJ, Mennicken C, de Graaf DM, Shkarina K, Wagner T, Latz E. Western lifestyle linked to maladaptive trained immunity. Elife. 2026 Jan 21;15:e105835. doi: 10.7554/eLife.105835. PMID: 41563898; PMCID: PMC12823064.
Project A11 Publications 2nd Funding Period 2024 - 2027
2024
Wang W, Dernst A, Martin B, Lorenzi L, Cadefau-Fabregat M, Phulphagar K, Wagener A, Budden C, Stair N, Wagner T, Färber H, Jaensch A, Stahl R, Duthie F, Schmidt SV, Coll RC, Meissner F, Cuartero S, Latz E, Mangan MSJ. Butyrate and propionate are microbial danger signals that activate the NLRP3 inflammasome in human macrophages upon TLR stimulation. Cell Rep. 2024 Sep 13;43(9):114736. doi: 10.1016/j.celrep.2024.114736. Epub ahead of print. PMID: 39277863.
Weiss FD, Alvarez Y, Shakeri F, Sahu A, Leka P, Dernst A, Rollheiser J, Vasconcelos M, Geraci A, Duthie F, Stahl R, Lee HE, Gellner AK, Buness A, Latz E, Meissner F. Retention of ES cell-derived 129S genome drives NLRP1 hypersensitivity and transcriptional deregulation in Nlrp3tm1Flv mice. Cell Death Differ. 2024 Sep 17. doi: 10.1038/s41418-024-01379-2. Epub ahead of print. PMID: 39289506.
Project related Publications
2010 - 2023
Nickenig, M., Mangan, M.S.J., Lee, H.E., Symeonidis, K., Henne, A., Kaiser, R., Geißmar, E., Garritsen, H., Abdullah, Z., Hiller, K., Latz, E., and Lauterbach, M.A. (2024). Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1. J Immunol. 2024 212, 7-11. doi: 10.4049/jimmunol.2200835.
Próchnicki, T., Vasconcelos, M.B., Robinson, K.S., Mangan, M.S.J., De Graaf, D., Shkarina, K., Lovotti, M., Standke, L., Kaiser, R., Stahl, R., Duthie, F.G., Rothe, M., Antonova, K., Jenster, L.M., Lau, Z.H., Rösing, S., Mirza, N., Gottschild, C., Wachten, D., Günther, C., Kufer, T.A., Schmidt, F.I., Zhong, F.L., and Latz, E. (2023). Mitochondrial damage activates the NLRP10 inflammasome. Nat Immunol. 24, 595-603
Zhen,. D., Mohapatra, G., Kern, L., He, Y., Shmueli, M.D., Valdés-Mas, R., Kolodziejczyk, A., Próchnicki, T., Vasconcelos, M.B., Puschhof, J., Schorr, L., Hertel, F., Camacho, M., Cheddaha, C.M., Shimshy, S., Hodgetts, R.J., Dori-Bachash, M., Kleimeyer, C., Goldenberg, K., Heinemann, M., Stettner, N., Harmelin, A., Shapiro, H., Chen, M., Abdeen, S.K., Latz,E., Merbl, Y., and Elinav, E. (2023). Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation. Nat Immunol. 24, 585-594
Budden, C.F., Gearing, L.J., Kaiser, R., Standke, L., Hertzog, P.J., and Latz, E. (2021). Inflammasome-induced extracellular vesicles harbor distinct RNA signatures and alter bystander macrophage responses. J Extracell Vesicles. 10, e12127.
Hochheiser, I.V., Pilsl, M., Hagelueken, G., Moecking, J., Marleaux, M., Brinkschulte, R., Latz, E, Engel, C., and Geyer, M. (2022). Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature 604, 184-189.
Hoss, F., Mueller, J.L., Rojas Ringeling, F., Rodriguez-Alcazar, J.F., Brinkschulte, R., Seifert, G., Stahl, R., Broderick, L., Putnam, C.D., Kolodner, R.D., Canzar, S., Geyer, M., Hoffman, H.M., and Latz, E. (2019). Alternative splicing regulates stochastic NLRP3 activity. Nat Commun.10, 3238.
Christ, A., Gunther, P., Lauterbach, M.A.R., Duewell, P., Biswas, D., Pelka, K., Scholz, C.J., Oosting, M., Haendler, K., Baßler, K., Klee, K., Schulte-Schrepping, J., Ulas, T., Moorlag, S.J.C.F.M., Kumar, V., Park, M.H., Joosten, L.A.B., Groh, L.A., Riksen, N.P., Espevik, T., Schlitzer, A., Li, Y., Fitzgerald, M.L., Netea, M.G., Schultze, J.L., and Latz, E. (2018). Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 172, 162-175.
Stutz, A., Kolbe, C.C., Stahl, R., Horvath, G.L., Franklin, B.S., van Ray, O., Brinkschulte, R., Geyer, M., Meissner, F., and Latz, E. (2017). NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain. J Exp Med. 214, 1725-1736.
Franklin, B.S., Bossaller, L., De Nardo, D., Ratter, J.M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S.R., Al-Amoudi, A., Mangan, M.S., Zimmer, S., Monks, B.G., Fricke, M., Schmidt, R.E., Espevik, T., Jones, B., Jarnicki, A.G., Hansbro, P.M., Busto, P., Marshak-Rothstein, A., Hornemann, S., Aguzzi, A., Kastenmuller, W., and Latz, E. (2014). The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation. Nat. Immunol.15, 727-737.
Duewell, P., Kono, H., Rayner, K.J., Sirois, C.M., Vladimer, G., Bauernfeind, F.G., Abela, G.S., Franchi, L., Nunez, G., Schnurr, M., Espevik, T., Lien, E., Fitzgerald, K.A., Rock, K.L., Moore, K.J., Wright, S.D., Hornung, V., and Latz, E. (2010). NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357-1361.