Molecular and functional studies on the crosstalk between induced IEL and IECs in intestinal homeostasis and inflammation
Project Summary
Induced intraepithelial lymphocytes (IELs) are widespread within the intestinal epithelial cell (IEC) layer. However, their differentiation and function under healthy conditions, as well as their role in the pathogenesis of inflammatory bowel diseases, remain to be fully elucidated. We have found that specific defects within the conventional dendritic cell (cDC1) compartment lead to marked alterations in the IEL population. Therefore, we aim to investigate the molecular mechanisms and functional consequences of IEL–IEC communication during intestinal homeostasis and inflammation by using cDC1-targeted mice as model systems for IEL deficiency.
Selected project-relevant publications
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.
Erkert L, Kabisch M, Gamez-Belmonte R, Gonzalez-Acera M, Patankar JV, Schödel L, Hofmann K, Wagner Y, Plattner C, Spath EM, Distler U, Tenzer S; TRR241 IBDome Consortium; Neufert C, Neurath MF, Becker C.
Pharmacological inhibitors of the gamma-secretase enzyme complex disrupt epithelial cell function triggering colitis in mice.
J Crohns Colitis. 2025 Jun 12:jjaf096. doi: 10.1093/ecco-jcc/jjaf096.
Weber S, Sitte S, Voegele AL, Sologub L, Wilfer A, Rath T, Nägel A, Zundler S, Franchi L, Opipari AW, Sonnewald S, Reid S, Hartmann A, Eichhorn P, Handtrack C, Weber K, Grützmann R, Neufert C, Schellerer VS, Naschberger E, Ekici AB, Büttner C, Neurath MF, Atreya R.
NLRP3 Inhibition Leads to Impaired Mucosal Fibroblast Function in Patients with Inflammatory Bowel Diseases.
J Crohns Colitis. 2024 Mar 1;18(3):446-461. doi: 10.1093/ecco-jcc/jjad164. PMID: 37748021.
Thoma OM, Naschberger E, Kubánková M, Larafa I, Kramer V, Menchicchi B, Merkel S, Britzen-Laurent N, Jefremow A, Grützmann R, Koop K, Neufert C, Atreya R, Guck J, Stürzl M, Neurath MF, Waldner MJ.
p21 Prevents the Exhaustion of CD4+ T Cells Within the Antitumor Immune Response Against Colorectal Cancer.
Gastroenterology. 2024 Feb;166(2):284-297.e11. doi: 10.1053/j.gastro.2023.09.017. Epub 2023 Sep 19. PMID: 37734420.
Guliev RR, Vogler T, Arend N, Eiserloh S, Wiede A, Kunert T, Dinkel M, Popp J, Schie IW, Hildner K, Neugebauer U.
High-throughput Raman spectroscopy allows ex vivo characterization of murine small intestinal intra-epithelial lymphocytes (IEL).
Analyst. 2023 May 2;148(9):1978-1990. doi: 10.1039/d3an00074e. PMID: 37000525.
Heidbreder K, Sommer K, Wiendl M, Müller TM, Atreya I, Hildner K, Neurath MF, Zundler S.
Nr4a1-dependent non-classical monocytes are important for macrophage-mediated wound healing in the large intestine.
Front Immunol. 2023 Jan 18;13:1040775. doi: 10.3389/fimmu.2022.1040775. PMID: 36741412; PMCID: PMC9890957.
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.
Kreiss L, Thoma OM, Lemire S, Lechner K, Carlé B, Dilipkumar A, Kunert T, Scheibe K, Heichler C, Merten AL, Weigmann B, Neufert C, Hildner K, Vieth M, Neurath MF, Friedrich O, Schürmann S, Waldner MJ.
Label-Free Characterization and Quantification of Mucosal Inflammation in Common Murine Colitis Models With Multiphoton Imaging.
Inflamm Bowel Dis. 2022 Nov 2;28(11):1637-1646. doi: 10.1093/ibd/izac114. PMID: 35699622; PMCID: PMC9629455.