P24 Prof. Dr. Latz/Dr. Ludwig-Portugall
Role of inflammasome activation in lupus nephritis

The goal of this project is to elucidate the role of inflammasome activation in lupus nephritis that is mediated by e.g. immune complex deposition in the glomeruli, local IL-1β production and TLR activation causing glomerular sclerosis. Using the pristane-induced mouse model for SLE, we will determine if inflammasome activation in specific cell types and at specific disease steps is important. A novel and potent small molecule inhibitor of NLRP3 will be used to assess efficacy of a novel treatment approach in our preclinical model. We will also address the question if renal MDSC are important regulators in glomerular sclerosis and translational aspects will focus on the identification of novel biomarkers for the determination of inflammasome activation during lupus disease progression in mouse and human samples. [...]

Publications

• Martin-Higueras C. , Ludwig-Portugall I., Hoppe B., Kurts C. (2019): Targeting kidney inflammation as a new therapy for Primary Hyperoxaluria?. Nephrol Dial Transpl, 34(6), 908-914, [4.198]
• Li T. , Zehner M., He J., Próchnicki T., Horvath G., Latz E., Burgdorf S., Takeoka S. (2019): NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells. International Journal of Nanomedicine, 14, 3503-3516, [4.471]
• Krishnan S. M. , Ling Y. H., Huuskes B. M., Ferens D. M., Saini N., Chan C. T., Diep H., Kett M. M., Samuel C. S., Kemp-Harper B. K., Robertson A. A. B, Cooper M. A., Peter K., Latz E., Mansell A. S., Sobey C. G., Drummond G. R., Vinh A. (2019): Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension. Cardiovascular Research, 115(4), 776-787, [7.014]
• He J. , Li T., Próchnicki T., Horvath G., Latz E., Takeoka S. (2019): Membrane Fusogenic Lysine Type Lipid Assemblies Possess Enhanced NLRP3 Inflammasome Activation Potency. Biochemistry and Biophysics Reports, 18, 100623, [1.650]
• Christ A. , Lauterbach M., Latz E. (2019): Western Diet and the Immune System: An Inflammatory Connection. Immunity, 51(5), 794-811, [21.522]
• Christ A. , Latz E. (2019): The Western lifestyle has lasting effects on metaflammation. Nature Reviews immunology, 19, 267-268, [44.019]
• Gotot J. , Dhana E., Yagita H., Kaiser R., Ludwig-Portugall I., Kurts C. (2018): Antigen-specific Helios–, Neuropilin-1– Tregs induce apoptosis of autoreactive B cells via PD-L1. Immunol Cell Biol, 96(8), 852-862, [3.947]
• Lehmann J. M. , Claus K., Jansen C., Pohlmann A., Schierwagen R., Meyer C., Thomas D., Manekeller S., Claria J., Strassburg C. P., Trautwein C., Wasmuth H. E., Berres M. L., Trebicka J. (2018): Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality. Liver Int, 38(5), 875-884, [5.542]
• Rolfes V. , Idel C., Pries R., Plötze-Martin K., Habermann J., Gemoll T., Bohnet S., Latz E., Ribbat-Idel J., Franklin B. S., Wollenberg B. (2018): PD-L1 is expressed on human platelets and is affected by immune checkpoint therapy. Oncotarget, 9, 27460-27470, [5.168]
• Pelka K. , Bertheloot D., Reimer E., Phulphagar K., Schmidt S. V., ChristA., Stahl R., Watson N., Miyake K., Hacohen N., Haas A., Brinkmann M. M., Marshak-Rothstein A., Meissner F., Latz E. (2018): The Chaperone UNC93B1 Regulates Toll-like Receptor Stability Independently of Endosomal TLR Transport. Immunity, 48(5), 911-922, [21.522]
• Mangan M. S. J. , Olhava E. J., Roush W. R., Seidel H. M., Glick G. D., Latz E. (2018): Targeting the NLRP3 inflammasome in inflammatory diseases. Nature reviews drug discovery, 17, 588-606, [57.618]
• Latz E. , Duewella P. (2018): NLRP3 inflammasome activation in inflammaging. Seminars in Immunology, 40, 61-73, [7.358]
• Labzin L. I. , Heneka M. T., Latz E. (2018): Innate Immunity and Neurodegeneration. Annual Review of Medicine, 69, 437-449, [10.091]
• Jansen C. , Möller P., Meyer C., Kolbe C. C., Bogs C., Pohlmann A., Schierwagen R., Praktiknjo M., Abdullah Z., Lehmann J., Thomas D., Strassburg C. P., Latz E., Mueller S., Rössle M., Trebicka J. (2018): Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality. Hepatology, 67(4), 1472-1484, [14.079]
• Heneka M. T. , McManus R. M., Latz E. (2018): Inflammasome signalling in brain function and neurodegenerative disease. Nature Reviews Neuroscience, 19, 610-621, [33.162]
• Grebe A. , Hoss F., Latz E. (2018): NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. Circulation Research, 122(12), 1722-1740, [15.862]
• Franklin B. S. , Mangan M. S., Latz E. (2018): Crystal Formation in Inflammation. Annual Reviews of Immunology, 34, 173-202, [21.429]
• Franklin B. S. , Latz E., Schmidt F. I. (2018): The intra- and extracellular functions of ASC specks. Immunological Reviews, 281(1), 74-87, [11.292]
• De Nardo D. , Balka K. R., Gloria Y. C., Rao‖ V. R., Latz E., Masters S. L. (2018): Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling. Journal of Biological Chemistry, 293, 15195-15207, [5.328]
• Christ A. , Günther 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., Latz E. (2018): Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell, 172 (1-2), 162-175, [32.304]
• Dhana E. , Ludwig-Portugall I., Kurts C. (2017): Role of immune cells in crystal-induced kidney fibrosis.. Mat Biol, 68-69, 280-292, [6.986]
• Klingberg A. , Hasenberg A., Ludwig-Portugall I., Medyukhina A., Männ L., Brenzel A., Engel D. R., Figge M. T., Kurts C., Gunzer M. (2017): Fully automated evaluation of total glomerular number and capillary tuft size in murine nephritic kidneys using lightsheet microscopy. J Am Soc Nephrol, 28(2), 452-459, [8.547]
• Zimmer S. , Grebe A, Bakke SS, Bode N, Halvorsen B, Ulas T, Skjelland M, De Nardo D, Labzin LI, Kerksiek A, Hempel C, Heneka MT, Hawxhurst V, Fitzgerald ML, Trebicka J, Björkhem I, Gustafsson JÅ, Westerterp M, Tall AR, Wright SD, Espevik T, Schultze JL, Nickenig G, Lütjohann D, Latz E. (2016): Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Sciience Translational Medicine, 8 (333), 333ra50, [16.264]
• Labzin, L.I. , Lauterbach, M.A.R., Latz, E. (2016): Interferons and inflammasomes: Cooperation and counterregulation in disease. Journal of Allergy and Clinical Immunology, 1, 37-46, [12.485]
• Schierwagen R , Maybüchen L, Hittatiya K, Klein S, Uschner FE, Braga TT, Franklin BS, Nickenig G, Strassburg CP, Plat J, Sauerbruch T, Latz E, Lütjohann D, Zimmer S, Trebicka J (2016): Statins improve NASH via inhibition of RhoA and Ras. Liver Physiology, 311(4), 724-733, [3.297]
• von Kolontaj, K. , Horvath, G. L., Latz, E., Büscher, M. (2016): Automated nanoscale flow cytometry for assessing protein-protein interactions. Cytometry Part A, 89(9), 835–843, [3.181]
• Horr, F. , Rodriguez-Alcazar, J. F., Latz, E (2016): Assembly and regulation of ASC specks. Cellular and Molecular Life Sciences, 74(7), 1211–1229, [5.694]
• Evers B.D.G. , Engel D.R., Böhner A.M.C., Tittel A.P., Krause T.A., Heuser C., Garbi N., Kastenmüller W., Mack M., Tiegs G., Panzer U., Boor P., Ludwig-Portugall I., Kurts C. (2016): CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10–Producing Regulatory T Cells. Journal of the American Society of Nephrology, 27(11), 3368-3382, [8.491]
• Bossaller, L , Christ, A., Pelka, K., Nündel, K., Chiang, P.-I., Pang, C., Mishra, N., Busto, P., Bonegio, R.G., Schmidt, R.E., Latz, E., Marshak-Rothsteinet, A. (2016): TLR9 Deficiency Leads to Accelerated Renal Disease and Myeloid Lineage Abnormalities in Pristane-Induced Murine Lupus. Journal of Immunology, 197 (4), 1044–1053, [4.985]
• Bertheloot, D. , Latz, E. (2016): HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins. Cellular & Molecular Immunology, 14 (1), 43-64, [5.193]
• Schneider, K. M. , Bieghs V., Heymann F., Hu W., Dreymueller D., Liao L., Frissen M., Ludwig A., Gassler N., Pabst O., Latz E., Sellge G., Penders J., Tacke F., Trautwein C. (2015): CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis.. Hepatology, 62 (5), 1405-1416, [11.711]
• Hoechst, B. , Mikulec ,J., Baccega, T., Metzger, C., Welz, M., Peusquens, J., Tacke, F., Knolle, P., Kurts, C., Diehl, L., Ludwig-Portugall, I. (2015): Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis.. PLoS One, 10 (3) e0119662, [3.057]
• Heymann, F. , Peusquens, J., Ludwig-Portugall, I., Kohlhepp, M., Ergen, C., Niemietz, P., Martin, C., van Rooijen, N., Ochando, J.C., Randolph, G.J., Luedde, T., Ginhoux, F., Kurts, C., Trautwein, C., Tacke, F (2015): Liver inflammation abrogates immunological tolerance induced by Kupffer cells.. Hepatology, 62 (1), 279-91, [11.711]
• Coll, R. C. (2015): A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.. Nat Med, [28.220]
• Gottschalk, C. , Damuzzo, V., Gotot, J., Kroczek, R.A., Yagita, H., Murphy, K.M., Knolle, P.A., Ludwig-Portugall, I., Kurts, C. (2013): Batf3-dependent dendritic cells in the renal lymph node induce tolerance against circulating antigens.. Journal of the American Society of Nephrology, 24 (4), 543-549, [8.491]
• Bossaller, L. , Rathinam, V. A., Bonegio, R., Chiang, P. I., Busto, P., Wespiser, A. R., Caffrey, D. R., Li, Q. Z., Mohan, C., Fitzgerald, K. A., Latz, E., Marshak-Rothstein, A. (2013): Overexpression of membrane-bound fas ligand (CD95L) exacerbates autoimmune disease and renal pathology in pristane-induced lupus.. The Journal of Immunology, 191 (5), 2104-2114, [4.179]
• Bossaller, L. , Chiang, P. I., Schmidt-Lauber, C., Ganesan, S., Kaiser, W. J., Rathinam, V. A., Mocarski, E. S., Subramanian, D., Green, D. R., Silverman, N., Fitzgerald, K. A., Marshak-Rothstein, A., Latz, E. (2012): Cutting edge: FAS (CD95) mediates noncanonical IL-1beta and IL-18 maturation via caspase-8 in an RIP3-independent manner. Journal of Immunology, 189, 5508-5512, [4.179]
• Ooi, J. D. , Snelgrove, S. L., Engel, D. R., Hochheiser, K., Ludwig-Portugall, I., Nozaki, Y., O'Sullivan, K. M., Hickey, M. J., Holdsworth, S. R., Kurts, C., Kitching, A. R. (2011): Endogenous foxp3(+) T-regulatory cells suppress anti-glomerular basement membrane nephritis. Kidney International, 79 (9), 977-986, [7.683]