A07
The Mevalonate pathway as a checkpoint for regulation of prenylation within intestinal epithelial cells in the context of inflammation
Project Summary
Our project aims to improve the understanding of how protein prenylation is regulated in intestinal epithelial cells and how it contributes to epithelial integrity in the context of inflammatory bowel diseases. In particular, we seek to explore the dependence of intestinal homeostasis on the mevalonate pathway (MVP) in epithelial cells, as well as the context-specific regulation of its key enzyme HMG-CoA reductase (HMGCR) in the inflamed gut. By gaining new insights into the interplay between intestinal immune cells, MVP components in epithelial cells, and regulators of epithelial integrity, we aim to determine the relevance of the MVP as a source of novel therapeutic targets in IBD and to better understand the potential impact of statin co-medication on disease progression in IBD patients.
Selected project-relevant publications
Wiendl M, Dedden M, Liu LJ, Schweda A, Paap EM, Ullrich KA, Hartmann L, Wieser L, Vitali F, Atreya I, Müller TM, Günther C, Atreya R, Neurath MF, Zundler S.
Etrolizumab-s fails to control E-Cadherin-dependent co-stimulation of highly activated cytotoxic T cells.
Nat Commun. 2024 Feb 3;15(1):1043. doi: 10.1038/s41467-024-45352-6. PMID: 38310086; PMCID: PMC10838339.
Schulz-Kuhnt A, Rühle K, Javidmehr A, Döbrönti M, Biwank J, Knittel S, Neidlinger P, Leupold J, Liu LJ, Dedden M, Taudte RV, Gessner A, Fromm MF, Mielenz D, Kreiss L, Waldner MJ, Schürmann S, Friedrich O, Dietel B, López-Posadas R, Plattner C; TRR241 IBDome Consortium; Zundler S, Becker C, Atreya R, Neurath MF, Atreya I.
ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.
Gut. 2024 Mar 7;73(4):601-612. doi: 10.1136/gutjnl-2023-330543. PMID: 38176897.
Sommer K, Heidbreder K, Kreiss L, Dedden M, Paap EM, Wiendl M, Becker E, Atreya R, Müller TM, Atreya I, Waldner M, Schürmann S, Friedrich O, Neurath MF, Zundler S.
Anti-β7 integrin treatment impedes the recruitment on non-classical monocytes to the gut and delays macrophage-mediated intestinal wound healing.
Clin Transl Med. 2023 Apr;13(4):e1233. doi: 10.1002/ctm2.1233. PMID: 37029786; PMCID: PMC10082567.
Ullrich KA, Derdau J, Baltes C, Battistella A, Rosso G, Uderhardt S, Schulze LL, Liu LJ, Dedden M, Spocinska M, Kainka L, Kubánková M, Müller TM, Schmidt NM, Becker E, Ben Brahim O, Atreya I, Finotto S, Prots I, Wirtz S, Weigmann B, López-Posadas R, Atreya R, Ekici AB, Lautenschläger F, Guck J, Neurath MF, Zundler S.
IL-3 receptor signalling suppresses chronic intestinal inflammation by controlling mechanobiology and tissue egress of regulatory T cells.
Gut. 2023 Nov;72(11):2081-2094. doi: 10.1136/gutjnl-2023-329818. Epub 2023 Aug 4. PMID: 37541770; PMCID: PMC10579496.
Müller TM, Liu LJ, Czerwinski T, Wiesinger M, Dedden M, Paap EM, Ullrich KA, Atreya I, Siegmund B, Atreya R, Fabry B, Berking C, Neurath MF, Zundler S, Voskens CJ.
Increased Motility and Suppression of Ex Vivo-Expanded Regulatory T Cells Designed for Adoptive Transfer Therapy in Ulcerative Colitis.
Cell Mol Gastroenterol Hepatol. 2023;16(1):183-187.e2. doi: 10.1016/j.jcmgh.2023.04.002. Epub 2023 Apr 20. Erratum in: Cell Mol Gastroenterol Hepatol. 2025 Jun 6:101554. doi: 10.1016/j.jcmgh.2025.101554. PMID: 37085136; PMCID: PMC10285232.
Schneider I, Allner C, Mühl L, Melde M, Lissner D, Mantzivi E, Glauben R, Vitali F, Becker E, Atreya I, Müller TM, Atreya R, Siegmund B, Neurath MF, Zundler S.
Expression and function of α4β7 integrin predict the success of vedolizumab treatment in inflammatory bowel disease.
Transl Res. 2023 Mar;253:8-15. doi: 10.1016/j.trsl.2022.10.003. Epub 2022 Oct 20. PMID: 36272713.
Martínez-Sánchez LDC, Ngo PA, Pradhan R, Becker LS, Boehringer D, Soteriou D, Kubankova M, Schweitzer C, Koch T, Thonn V, Erkert L, Stolzer I, Günther C, Becker C, Weigmann B, Klewer M, Daniel C, Amann K, Tenzer S, Atreya R, Bergo M, Brakebusch C, Watson AJM, Guck J, Fabry B, Atreya I, Neurath MF, López-Posadas R.
Epithelial RAC1-dependent cytoskeleton dynamics controls cell mechanics, cell shedding and barrier integrity in intestinal inflammation.
Gut. 2023 Feb;72(2):275-294. doi: 10.1136/gutjnl-2021-325520. Epub 2022 Mar 3. PMID: 35241625; PMCID: PMC9872254.
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.
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.
Soteriou D, Kubánková M, Schweitzer C, López-Posadas R, Pradhan R, Thoma OM, Györfi AH, Matei AE, Waldner M, Distler JHW, Scheuermann S, Langejürgen J, Eckstein M, Schneider-Stock R, Atreya R, Neurath MF, Hartmann A, Guck J.
Rapid single-cell physical phenotyping of mechanically dissociated tissue biopsies.
Nat Biomed Eng. 2023 Nov;7(11):1392-1403. doi: 10.1038/s41551-023-01015-3. Epub 2023 Apr 6. PMID: 37024677; PMCID: PMC10651479.
Besendorf L, Müller TM, Geppert CI, Schneider I, Mühl L, Atreya I, Vitali F, Atreya R, Neurath MF, Zundler S.
Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis.
Therap Adv Gastroenterol. 2022 Jun 28;15:17562848221098899. doi: 10.1177/17562848221098899. PMID: 35784193; PMCID: PMC9244938.