Emergency barriers in Inflammatory Bowel Diseases – Neutrophil-epithelial crosstalk shapes epithelial restitution in the ulcer microenvironment
Project Summary
Neutrophil extracellular traps (NETs) initiate plasma coagulation and form emergency barriers on mucosal wounds, possessing both antimicrobial and highly cytotoxic properties. We have discovered that NETs are actively involved in regulating mucosal healing responses. Regenerating epithelial tissues employ protective mechanisms to shield themselves from NET-associated cytotoxic mediators. This project focuses on these epithelial defense strategies, particularly those mediated by specialized epithelial cells. In the long term, we aim to explore therapeutic approaches targeting NET–epithelial imbalances to promote mucosal healing in patients with inflammatory bowel disease.
Selected project-relevant publications
Roth D, Düll MM, Horst LJ, Lindemann A, Malzer X, Koop K, Zundler S, Vetter M, Jefremow A, Atreya R, Geppert C, Weidemann S, Waldner MJ, Dietrich P, Günther C, Munoz LE, Herrmann M, Scheffold A, Neurath MF, Siebler J, Schramm C, Kremer AE, Leppkes M.
Integrin αVβ6: Autoantigen and Driver of Epithelial Remodeling in Colon and Bile Ducts in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.
J Crohns Colitis. 2025 Feb 4;19(2):jjae131. doi: 10.1093/ecco-jcc/jjae131.
Gonzalez-Acera M, Patankar JV, Erkert L, Cineus R, Gamez-Belmonte R, Leupold T, Bubeck M, Bao LL, Dinkel M, Wang R, Schickedanz L, Limberger H, Stolzer I, Gerlach K, Diemand L, Mascia F, Gupta P, Naschberger E, Koop K, Plattner C, Sturm G, Weigmann B, Günther C, Wirtz S, Stürzl M, Hildner K, Kühl AA, Siegmund B, Gießl A, Atreya R; TRR241 IBDome Consortium; Hegazy AN, Trajanoski Z, Neurath MF, Becker C.
Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD.
Gut. 2025 Apr 29:gutjnl-2024-333729. doi: 10.1136/gutjnl-2024-333729.
Hecker J, Plattner C, Cancino CA, Löscher BS, Saurenbach J, Letizia M, Rieder D; TRR241 IBDome Consortium; Freise I, Koop K, Neufert C, Kunkel D, Al Khatim Z, Schaafs LA, Schütz A, Becker C, Atreya R, Trajanoski Z, Franke A, Sonnenberg E, Hegazy AN, Siegmund B, Weidinger C.
IL-36 signaling as a drug target in Crohn’s disease patients with IL36RN mutations.
EMBO Mol Med. 2025 May 30. doi: 10.1038/s44321-025-00245-z.
Dorner H, Stolzer I, Mattner J, Kaminski S, Leistl S, Edrich LM, Schwendner R, Hobauer J, Sebald A, Leikam S, Gonzalez Acera M, Düll M, Lang R, Seidel G, Seitz T, Hellerbrand C, Fuhrmann G, Distler U, Tenzer S, Eichhorn P, Vieth M, Schramm C, Arnold P, Becker C, Weidinger C, Siegmund B, Atreya R, Leppkes M, Naschberger E, Sampaziotis F, Dietrich P, Rauh M, Wirtz S, Kremer AE, Neurath MF, Günther C.
Gut Pathobiont-Derived Outer Membrane Vesicles Drive Liver Inflammation and Fibrosis in Primary Sclerosing Cholangitis-Associated Inflammatory Bowel Disease.
Gastroenterology. 2024 Nov;167(6):1183-1197.e16. doi: 10.1053/j.gastro.2024.06.032. Epub 2024 Jul 9. PMID: 38992449.
Zlatar L, Knopf J, Singh J, Wang H, Muñoz-Becerra M, Herrmann I, Chukwuanukwu RC, Eckstein M, Eichhorn P, Rieker RJ, Naschberger E, Burkovski A, Krenn V, Bilyy R, Butova T, Liskina I, Kalabukha I, Khmel O, Boettcher M, Schett G, Butov D, Tkachenko A, Herrmann M.
Neutrophil extracellular traps characterize caseating granulomas.
Cell Death Dis. 2024 Jul 31;15(7):548. doi: 10.1038/s41419-024-06892-3. PMID: 39085192; PMCID: PMC11291884.
Schulze LL, Becker E, Dedden M, Liu LJ, van Passen C, Mohamed-Abdou M, Müller TM, Wiendl M, Ullrich KAM, Atreya I, Leppkes M, Ekici AB, Kirchner P, Stürzl M, Sexton D, Palliser D, Atreya R, Siegmund B; TRR241 IBDome consortium; Neurath MF, Zundler S.
Differential Effects of Ontamalimab Versus Vedolizumab on Immune Cell Trafficking in Intestinal Inflammation and Inflammatory Bowel Disease.
J Crohns Colitis. 2023 Nov 24;17(11):1817-1832. doi: 10.1093/ecco-jcc/jjad088. PMID: 37208197.
Cao X, Li Y, Luo Y, Chu T, Yang H, Wen J, Liu Y, Zhao Y, Herrmann M.
Transient receptor potential melastatin 2 regulates neutrophil extracellular traps formation and delays resolution of neutrophil-driven sterile inflammation.
J Inflamm (Lond). 2023 Feb 21;20(1):7. doi: 10.1186/s12950-023-00334-1. PMID: 36810113; PMCID: PMC9945693.
Koop K, Enderle K, Hillmann M, Ruspeckhofer L, Vieth M, Sturm G, Trajanoski Z, Kühl AA, Atreya R, Leppkes M, Baum P, Roy J, Martin A, Neurath MF, Neufert C.
Interleukin 36 receptor-inducible matrix metalloproteinase 13 mediates intestinal fibrosis.
Front Immunol. 2023 May 3;14:1163198. doi: 10.3389/fimmu.2023.1163198. PMID: 37207229; PMCID: PMC10189878.
Wang H, Stehr AM, Singh J, Zlatar L, Hartmann A, Evert K, Naschberger E, von Stillfried S, Boor P, Muñoz LE, Knopf J, Stürzl M, Herrmann M.
Anti-DNA-IgM Favors the Detection of NET-Associated Extracellular DNA.
Int J Mol Sci. 2023 Feb 17;24(4):4101. doi: 10.3390/ijms24044101. PMID: 36835515; PMCID: PMC9958910.
Singh J, Herrmann I, Mahajan A, Schauer C, Shan X, Hartmann A, Rieker RJ, Evert K, Falkeis C, Naschberger E, von Stillfried S, Boor P, Muñoz LE, Schett G, Herrmann M, Knopf J. A
Pleomorphic Puzzle: Heterogeneous Pulmonary Vascular Occlusions in Patients with COVID-19.
Int J Mol Sci. 2022 Dec 1;23(23):15126. doi: 10.3390/ijms232315126. PMID: 36499449; PMCID: PMC9739020.