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Research Group Prof. Dr. Dr. M. Herrmann

Reduction processes of aptotic cells in pathogenesis of autoimmunity

Head: Prof. Dr. med. Dr. rer. nat. Martin Herrmann

MSU-induced inflammation

Gouty arthritis is the most prevalent form of inflammatory arthropathy. It is triggered if uric acid converts in sodium-rich fluids into needle-shaped, pro-inflammatory monosodium urate (MSU) crystals. The latter provoke inflammation in joints and tissues. This process is regulated by the NALP3 inflammasome, which is activated by a drop in intracellular potassium and promotes maturation and secretion of the pro-inflammatory IL-1β. We propose that after phagocytosis of MSU crystals the resulting endosomes fuse intracellularly with acidic lysosomes. The low pH in the phagolysosomes causes a massive release of sodium and raises the intracellular osmolarity. The high ionic strength is balanced by passive water influx through aquaporins leading to cell swelling. This dilutes the intracellular potassium concentrations and activates the NALP3 inflammasome.

Resolution of MSU-induced inflammation

Acute gouty arthritis is a self-limiting process despite the presence of residual crystals during remission. For this enigma we propose the following model: Aggregated neutrophil extracellular traps (NETs) contribute to the resolution of MSU-induced inflammation. In the early phase of gouty arthritis, MSU crystals induce NETs and the release of pro-inflammatory mediators. In the late phase, NETs aggregate and form gouty tophi. The latter immobilize and inactivate the pro-inflammatory mediators by proteolysis. This interrupts the positive feedback-loop of neutrophil recruitment and mediator release and thus orchestrate the resolution of inflammation in the presence of residual MSU crystals. Currently, we are investigating the MSU-induced inflammation for bone erosion and the inflammatory potential of nano and microparticles. This work is performed in co-operation with the group of Markus Hoffmann.

Clearance of apoptotic cells

As further project we are working on the clearance of apoptotic cells and the importance of this process for the development of autoimmunity. We described that cultured macrophages and granulocytes isolated from Caucasian SLE patients display an impaired phagocytic phenotype in vitro. Interestingly, the differentiation into macrophages was reduced in SLE stem cell cultures. Much less macrophages differentiated from the CD34 positive stem cells of the peripheral blood and most of the SLE stem cell-derived macrophages showed reduced phagocytic capacity, were smaller, and died early. Furthermore, we reported for the first time in vivo clearance defects in the germinal centers of the lymph nodes and in the skin of patients with SLE after UV exposure.    
We are interested in membrane modifications of dying and dead cells in general. Some apoptotic cells escape early clearance and shrink because they lose membranes due to extensive shedding of blebs. It was unclear how apoptotic cells compensate for this massive loss of plasma membranes. We observed that during blebbing of apoptotic cells, their surface membrane loss is substituted by membranes from endoplasmic reticulum containing incompletely processed proteins and intracellular lipids. This mechanism explains the simultaneous appearance of preformed recognition structures for adaptor proteins known to be involved in clearance of dying and dead cells.

Selected publications of Prof. Dr. Dr. habil. Martin Herrmann

  • Simon D, Tascilar K, Schmidt K, Manger B, Weckwerth L, Sokolova M, Bucci L, Fagni F, Manger K, Schuch F, Ronneberger M, Hueber A, Steffen U, Mielenz D, Herrmann M, Harrer T, Kleyer A, Krönke G, Schett G: Humoral and Cellular Immune Responses to SARS-CoV-2 Infection and Vaccination in Autoimmune Disease Patients With B Cell Depletion. Arthritis Rheumatol. 2022;74(1): 33-37
  • Hohberger B, Hosari S, Wallukat G, Kunze R, Krebs J, Müller M, Hennig T, Lämmer R, Horn F, Muñoz LE, Herrmann M, Mardin C: Agonistic autoantibodies against ß2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients. PLoS ONE. 2021;16(5):
  • Hosari D, Hosari S, Mahajan A, Oreski L, Schoen J, Shan X, Singh J, Wang H, Yaykasli KO, Knopf J, Munoz LE, Schauer C, Herrmann M: NEUTROPHILS AND NETS AS ORCHESTRATORS OF INFLAMMATORY DISEASES Clin Exp Rheumatol. 2021;39(5): 1151-1152
  • Yaykasli KO, Schauer C, Muñoz LE, Mahajan A, Knopf J, Schett G, Herrmann M: Neutrophil Extracellular Trap-Driven Occlusive Diseases. Cells. 2021;10(9):
  • Vitkov L, Muñoz LE, Knopf J, Schauer C, Oberthaler H, Minnich B, Hannig M, Herrmann M: Connection between Periodontitis-Induced Low-Grade Endotoxemia and Systemic Diseases: Neutrophils as Protagonists and Targets. Int J Mol Sci. 2021;22(9):
  • Cossarizza A, Chang HD, Radbruch A, Abrignani S, Addo R, Akdis M, Andrä I, Andreata F, Annunziato F, Arranz E, Bacher P, Bari S, Barnaba V, Barros-Martins J, Baumjohann D, Beccaria CG, Bernardo D, Boardman DA, Borger J, Böttcher C, Brockmann L, Burns M, Busch DH, Cameron G, Cammarata I, Cassotta A, Chang Y, Chirdo FG, Christakou E, Čičin-Šain L, Cook L, Corbett AJ, Cornelis R, Cosmi L, Davey MS, De Biasi S, De Simone G, Del Zotto G, Delacher M, Di Rosa F, Santo JD, Diefenbach A, Dong J, Dörner T, Dress RJ, Dutertre CA, Eckle SBG, Eede P, Evrard M, Falk CS, Feuerer M, Fillatreau S, Fiz-Lopez A, Follo M, Foulds GA, Fröbel J, Gagliani N, Galletti G, Gangaev A, Garbi N, Garrote JA, Geginat J, Gherardin NA, Gibellini L, Ginhoux F, Godfrey DI, Gruarin P, Haftmann C, Hansmann L, Harpur CM, Hayday AC, Heine G, Hernández DC, Herrmann M, Hoelsken O, Huang Q, Huber S, Huber JE, Huehn J, Hundemer M, Hwang WYK, Iannacone M, Ivison SM, Jäck HM, Jani PK, Keller B, Kessler N, Ketelaars S, Knop L, Knopf J, Koay HF, Kobow K, Kriegsmann K, Kristyanto H, Krueger A, Kuehne JF, Kunze-Schumacher H, Kvistborg P, Kwok I, Latorre D, Lenz D, Levings MK, Lino AC, Liotta F, Long HM, Lugli E, MacDonald KN, Maggi L, Maini MK, Mair F, Manta C, Manz RA, Mashreghi MF, Mazzoni A, McCluskey J, Mei HE, Melchers F, Melzer S, Mielenz D, Monin L, Moretta L, Multhoff G, Muñoz LE, Muñoz-Ruiz M, Muscate F, Natalini A, Neumann K, Ng LG, Niedobitek A, Niemz J, Almeida LN, Notarbartolo S, Ostendorf L, Pallett LJ, Patel AA, Percin GI, Peruzzi G, Pinti M, Pockley AG, Pracht K, Prinz I, Pujol-Autonell I, Pulvirenti N, Quatrini L, Quinn KM, Radbruch H, Rhys H, Rodrigo MB, Romagnani C, Saggau C, Sakaguchi S, Sallusto F, Sanderink L, Sandrock I, Schauer C, Scheffold A, Scherer HU, Schiemann M, Schildberg FA, Schober K, Schoen J, Schuh W, Schüler T, Schulz AR, Schulz S, Schulze J, Simonetti S, Singh J, Sitnik KM, Stark R, Starossom S, Stehle C, Szelinski F, Tan L, Tarnok A, Tornack J, Tree TIM, van Beek JJP, van de Veen W, van Gisbergen K, Vasco C, Verheyden NA, von Borstel A, Ward-Hartstonge KA, Warnatz K, Waskow C, Wiedemann A, Wilharm A, Wing J, Wirz O, Wittner J, Yang JHM, Yang J: Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition). Eur J Immunol. 2021;51(12): 2708-3145
  • Hohberger B, Schlötzer-Schrehard U, Mardin C, Lämmer R, Munoz L, Kunze R, Herrmann M, Wallukat G: Inhibitory and Agonistic Autoantibodies Directed Against the β2-Adrenergic Receptor in Pseudoexfoliation Syndrome and Glaucoma. Front Neurosci. 2021;15():
  • Leppkes M, Lindemann A, Gößwein S, Paulus S, Roth D, Hartung A, Liebing E, Zundler S, Gonzalez-Acera M, Patankar JV, Mascia F, Scheibe K, Hoffmann M, Uderhardt S, Schauer C, Foersch S, Neufert C, Vieth M, Schett G, Atreya R, Kühl AA, Bleich A, Becker C, Herrmann M, Neurath MF: Neutrophils prevent rectal bleeding in ulcerative colitis by peptidyl-arginine deiminase-4-dependent immunothrombosis. Gut. 2021;():
  • Friščić J, Böttcher M, Reinwald C, Bruns H, Wirth B, Popp SJ, Walker KI, Ackermann JA, Chen X, Turner J, Zhu H, Seyler L, Euler M, Kirchner P, Krüger R, Ekici AB, Major T, Aust O, Weidner D, Fischer A, Andes FT, Stanojevic Z, Trajkovic V, Herrmann M, Korb-Pap A, Wank I, Hess A, Winter J, Wixler V, Distler J, Steiner G, Kiener HP, Frey B, Kling L, Raza K, Frey S, Kleyer A, Bäuerle T, Hughes TR, Grüneboom A, Steffen U, Krönke G, Croft AP, Filer A, Köhl J, Klein K, Buckley CD, Schett G, Mougiakakos D, Hoffmann MH: The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts. Immunity. 2021;54(5): 1002-1021.e10
  • Hoffmann-Vold AM, Allanore Y, Alves M, Brunborg C, Airó P, Ananieva LP, Czirják L, Guiducci S, Hachulla E, Li M, Mihai C, Riemekasten G, Sfikakis PP, Kowal-Bielecka O, Riccardi A, Distler O, EUSTAR collaborators , Cerinic MM, Walker U, Iannone F, Becvar R, Valentini G, Siegert E, Montecucco C, Carreira PE, Chizzolini C, Kucharz EJ, Doria A, Bancel PDF, Hesselstrand R, Balbir-Gurman A, Pellerito R, Caimmi C, Denton C, Damjanov N, Henes J, Heitmann VOS, Salvador MJ, Stamenkovic B, Selmi CF, Herrick A, Müller-Ladner U, Engelhart M, Riccieri V, Ionescu RM, Gheorghiu AM, Sunderkötter C, Distler J, Ingegnoli F, Mouthon L, Smith V, Cantatore FP, Ullman S, Pozzi MR, Wiland P, Vanthuyne M, Krummel-Lorenz B, Saar P, Herrmann K, Langhe E, Anic B, Baresic M, Mayer M, Yavuz S, Müller CS, Zenone T, Mathieu A, Vacca A, Solanki K, Rosato E, Oksel F, Yargucu F, Tanaseanu CM, Foti R, Furst DE, Villiger P, Adler S, de la Peña Lefebvre PG, González Martín JJ, Litinsky I, Galdo FD, Seskute G, Saketkoo LA, Kerzberg E, Castellví I, Spertini F, Hsu VM, Martin T, Schmeiser T, Bernardino DMV, Puttini PS: Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis. 2021;80(2): 219-227