B01

Mesenteric fat – an immunological barrier in Crohn’s disease?

Z02

B01

A09

Project Summary

Creeping fat is a characteristic pathological finding in Crohn’s disease, yet its impact on intestinal inflammation and epithelial barrier function remains poorly understood. This project aims to define how intestinal barrier defects shape the homeostasis of mesenteric fat, how these alterations contribute to the formation of an alternative barrier structure, and how creeping fat modulates epithelial resistance as well as the composition and immune activity of intestinal immune cells. A fat-depleting mouse model will be used to address these questions, and the findings will be correlated with data from a cohort of Crohn’s disease patients.

Selected project-relevant publications

Trajanoski Z, Plattner C, Sturm G, Kühl A, Atreya R, Carollo S, Gronauer R, Rieder D, Günther M, Ormanns S, Manzl C, Wirtz S, Meneghetti A, Hegazy A, Patankar J, Carrero Z, Neurath M, Kather J, Becker C, Siegmund B.
IBDome: An integrated molecular, histopathological, and clinical atlas of inflammatory bowel diseases.
Res Sq [Preprint]. 2025 May 6:rs.3.rs-6443303. doi: 10.21203/rs.3.rs-6443303/v1. PMID: 40386420; PMCID: PMC12083645.

Budzinski L, Kang GU, Riedel R, Sempert T, Lietz L, Maier R, Büttner J, Bochow B, Tordai MT, Shah A, Abbas A, Momtaz T, Krause JL, Kempkens R, Lehman K, Heinz GA, Benken AE, Bartsch S, Necke K, Hoffmann U, Mashreghi MF, Biesen R, Kallinich T, Alexander T, Jessen B, Weidinger C, Siegmund B, Radbruch A, Schirbel A, Moser B, Chang HD.
Single-cell microbiota phenotyping reveals distinct disease and therapy-associated signatures in Crohn’s disease.
Gut Microbes. 2025 Dec;17(1):2452250. doi: 10.1080/19490976.2025.2452250. Epub 2025 Jan 15. PMID: 39815413; PMCID: PMC11740678.

Bao LL, Yu YQ, González-Acera M, Patankar JV, Giessl A, Sturm G, Kühl AA, Atreya R, Erkert L, Gámez-Belmonte R, Krug SM, Schmid B, Tripal P, Chiriac MT, Hildner K, Siegmund B, Wirtz S, Stürzl M, Mohamed Abdou M, Trajanoski Z; TRR241 IBDome Consortium; Neurath MF, Zorzano A, Becker C.
Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.
Sci Transl Med. 2025 Jan 15;17(781):eadn8699. doi: 10.1126/scitranslmed.adn8699.

Horn V, Cancino CA, Steinheuer LM, Obermayer B, Fritz K, Nguyen AL, Juhran KS, Plattner C, Bösel D, Oldenburg L, Burns M, Schulz AR, Saliutina M, Mantzivi E, Lissner D, Conrad T, Mashreghi MF, Zundler S, Sonnenberg E, Schumann M, Haag LM, Beule D, Flatz L; TRR241 IBDome Consortium; Trajanoski Z, D’Haens G, Weidinger C, Mei HE, Siegmund B, Thurley K, Hegazy AN.
Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.
Gastroenterology. 2025 Feb;168(2):327-343. doi: 10.1053/j.gastro.2024.09.021.

Plattner C, Sturm G, Kühl AA, Atreya R, Carollo S, Gronauer R, Rieder D, Günther M, Ormanns S, Manzl C, Wirtz S, Meneghetti AR, Hegazy AN, Patankar JV, Carrero ZI; TRR241 IBDome Consortium; Neurath MF, Kather JN, Becker C, Siegmund B, Trajanoski Z.
IBDome: An integrated molecular, histopathological, and clinical atlas of inflammatory bowel diseases.
bioRxiv [Preprint]. 2025 Apr 10:2025.03.26.645544. doi: 10.1101/2025.03.26.645544.

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.

Avery EG, Haag LM, McParland V, Kedziora SM, Zigra GJ, Valdes DS, Kirchner M, Popp O, Geisberger S, Nonn O, Karlsen TV, N’Diaye G, Yarritu A, Bartolomaeus H, Bartolomaeus TUP, Tagiyeva NA, Wimmer MI, Haase N, Zhang YD, Wilhelm A, Grütz G, Tenstad O, Wilck N, Forslund SK, Klopfleisch R, Kühl AA, Atreya R, Kempa S, Mertins P, Siegmund B, Wiig H, Müller DN.
Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.
Cardiovasc Res. 2025 May 23;121(5):803-816. doi: 10.1093/cvr/cvae267.

Lehmann M, Paclik D, Huck A, Arnold A, Kurth-Stavenhagen C, Vieth M, Treese C, Kühl AA, Siegmund B.
Spatial immune profiling of Crohn’s disease fistula carcinomas-defining a distinct cancer subtype.
J Crohns Colitis. 2025 Jun 4;19(6):jjaf086. doi: 10.1093/ecco-jcc/jjaf086.

Cineus R, Luo Y, Saliutina M, Manna S, Cancino CA, Velasco Blázquez L, Wang L, Bösel D, Abdelrahman A, Klementowicz JE, Scherl A, Hainbuch S, Bréart B, Kwon G, Konopka A, Guerra GM, von Coburg E, Gerbeth L, Roels J, Heinrich F, Müller N, Durek P, Deigendesch N, Ziai J, Hung J, Conrad T; TRR241 IBDome Consortium; Kühl AA, Wirtz S, Löhning M, Keir M, Diefenbach A, Mashreghi MF, Siegmund B, Schumann M, Romagnani C, West NR, Hegazy AN.
The IL-22-oncostatin M axis promotes intestinal inflammation and tumorigenesis.
Nat Immunol. 2025 Jun;26(6):837-853. doi: 10.1038/s41590-025-02149-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.

Chiriac MT, Hracsko Z, Günther C, Gonzalez-Acera M, Atreya R, Stolzer I, Wittner L, Dressel A, Schickedanz L, Gamez-Belmonte R, Erkert L, Hundorfean G, Zundler S, Rath T, Vetrano S, Danese S, Sturm G, Trajanoski Z, Kühl AA, Siegmund B, Hartmann A, Wirtz S, Siebler J, Finotto S, Becker C, Neurath MF.
IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling.
Gut. 2024 Jan 5;73(2):282-297. doi: 10.1136/gutjnl-2023-329628. PMID: 37884352; PMCID: PMC10850655.

Wiese JJ, Manna S, Kühl AA, Fascì A, Elezkurtaj S, Sonnenberg E, Bubeck M, Atreya R, Becker C, Weixler B, Siegmund B, Patankar JV, Prüß MS, Schumann M.
Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn’s Disease and Ulcerative Colitis.
J Crohns Colitis. 2024 Jan 27;18(1):121-133. doi: 10.1093/ecco-jcc/jjad122. PMID: 37565754; PMCID: PMC10821712.

Almalla A, Alzain N, Elomaa L, Richter F, Scholz J, Lindner M, Siegmund B, Weinhart M.
Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models.
Cells. 2024 Jun 21;13(13):1080. doi: 10.3390/cells13131080. PMID: 38994934; PMCID: PMC11240340.

Essex M, Rios Rodriguez V, Rademacher J, Proft F, Löber U, Markó L, Pleyer U, Strowig T, Marchand J, Kirwan JA, Siegmund B, Forslund SK, Poddubnyy D.
Shared and Distinct Gut Microbiota in Spondyloarthritis, Acute Anterior Uveitis, and Crohn’s Disease.
Arthritis Rheumatol. 2024 Jan;76(1):48-58. doi: 10.1002/art.42658. Epub 2023 Oct 19. PMID: 37471465.

Lehmann M, Weixler B, Elezkurtaj S, Loddenkemper C; TRR241 IBDome Consortium; Kühl AA, Siegmund B.
Spatial Single Cell Profiling Using Imaging Mass Cytometry: Inflammatory Versus Penetrating Crohn’s Disease.
J Crohns Colitis. 2024 Aug 14;18(8):1305-1318. doi: 10.1093/ecco-jcc/jjae033. PMID: 38465390.

Martini GR, Tikhonova E, Rosati E, DeCelie MB, Sievers LK, Tran F, Lessing M, Bergfeld A, Hinz S, Nikolaus S, Kümpers J, Matysiak A, Hofmann P, Saggau C, Schneiders S, Kamps AK, Jacobs G, Lieb W, Maul J, Siegmund B, Seegers B, Hinrichsen H, Oberg HH, Wesch D, Bereswill S, Heimesaat MM, Rupp J, Kniemeyer O, Brakhage AA, Brunke S, Hube B, Aden K, Franke A, Iliev ID, Scheffold A, Schreiber S, Bacher P.
Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease.
Nat Med. 2023 Oct;29(10):2602-2614. doi: 10.1038/s41591-023-02556-5. Epub 2023 Sep 25. PMID: 37749331; PMCID: PMC10579100.

Mechsner S, Grünert J, Wiese JJ, Vormbäumen J, Sehouli J, Siegmund B, Neeb L, Prüß MS.
Transcranial direct current stimulation to reduce chronic pelvic pain in endometriosis: phase II randomized controlled clinical trial.
Pain Med. 2023 Jul 5;24(7):809-817. doi: 10.1093/pm/pnad031. PMID: 36882181.

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.

Wittner L, Wagener L, Wiese JJ, Stolzer I, Krug SM, Naschberger E, Jackstadt R, Beyaert R, Atreya R, Kühl AA, Sturm G, Gonzalez-Acera M, Patankar JV, Becker C, Siegmund B, Trajanoski Z, Winner B, Neurath MF, Schumann M, Günther C.
Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing.
Int J Mol Sci. 2023 Apr 17;24(8):7402. doi: 10.3390/ijms24087402. PMID: 37108564; PMCID: PMC10138456.

Voskens C, Stoica D, Rosenberg M, Vitali F, Zundler S, Ganslmayer M, Knott H, Wiesinger M, Wunder J, Kummer M, Siegmund B, Schnoy E, Rath T, Hartmann A, Hackstein H, Schuler-Thurner B, Berking C, Schuler G, Atreya R, Neurath MF.
Autologous regulatory T-cell transfer in refractory ulcerative colitis with concomitant primary sclerosing cholangitis.
Gut. 2023 Jan;72(1):49-53. doi: 10.1136/gutjnl-2022-327075. Epub 2022 Apr 15. PMID: 35428657; PMCID: PMC9763232.

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.

Rodríguez-Sillke Y, Schumann M, Lissner D, Branchi F, Proft F, Steinhoff U, Siegmund B, Glauben R.
Analysis of Circulating Food Antigen-Specific T-Cells in Celiac Disease and Inflammatory Bowel Disease.
Int J Mol Sci. 2023 May 2;24(9):8153. doi: 10.3390/ijms24098153. PMID: 37175860; PMCID: PMC10179603.

Friebel J, Schinnerling K, Weigt K, Heldt C, Fromm A, Bojarski C, Siegmund B, Epple HJ, Kikhney J, Moter A, Schneider T, Schulzke JD, Moos V, Schumann M.
Uptake of Tropheryma whipplei by Intestinal Epithelia.
Int J Mol Sci. 2023 Mar 24;24(7):6197. doi: 10.3390/ijms24076197. PMID: 37047170; PMCID: PMC10094206.

Ahlers J, Mantei A, Lozza L, Stäber M, Heinrich F, Bacher P, Hohnstein T, Menzel L, Yüz SG, Alvarez-Simon D, Bickenbach AR, Weidinger C, Mockel-Tenbrinck N, Kühl AA, Siegmund B, Maul J, Neumann C, Scheffold A.
A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4+ T cells and is defective in Crohn´s disease patients.
Mucosal Immunol. 2022 Mar;15(3):480-490. doi: 10.1038/s41385-022-00487-x. Epub 2022 Feb 15. PMID: 35169232; PMCID: PMC9038525.

Branchi F, Wiese JJ, Heldt C, Manna S, Dony V, Loddenkemper C, Bojarski C, Siegmund B, Schneider T, Daum S, Hummel M, Moos V, Schumann M.
The combination of clinical parameters and immunophenotyping of intraepithelial lymphocytes allows to assess disease severity in refractory celiac disease.
Dig Liver Dis. 2022 Dec;54(12):1649-1656. doi: 10.1016/j.dld.2022.06.024. Epub 2022 Jul 15. PMID: 35850920.

Prüß MS, Bayer A, Bayer KE, Schumann M, Atreya R, Mekle R, Fiebach JB, Siegmund B, Neeb L.
Functional Brain Changes Due to Chronic Abdominal Pain in Inflammatory Bowel Disease: A Case-Control Magnetic Resonance Imaging Study.
Clin Transl Gastroenterol. 2022 Feb 1;13(2):e00453. doi: 10.14309/ctg.0000000000000453. PMID: 35060939; PMCID: PMC8865502.

Hegazy AN, Krönke J, Angermair S, Schwartz S, Weidinger C, Keller U, Treskatsch S, Siegmund B, Schneider T.
Anti-SARS-CoV2 antibody-mediated cytokine release syndrome in a patient with acute promyelocytic leukemia.
BMC Infect Dis. 2022 Jun 13;22(1):537. doi: 10.1186/s12879-022-07513-0. PMID: 35692034; PMCID: PMC9188919.

Hecker J, Letizia M, Loescher BS, Siegmund B, Weidinger C.
Early Onset of TNFα-Driven Arthritis, Auto-inflammation, and Progressive Loss of Vision in a Patient with ALPK1 Mutation.
J Clin Immunol. 2022 May;42(4):880-884. doi: 10.1007/s10875-022-01214-8. Epub 2022 Mar 2. PMID: 35235128; PMCID: PMC9166835.

Atreya R, Bojarski C, Kühl AA, Trajanoski Z, Neurath MF, Siegmund B.
Ileal and colonic Crohn’s disease: Does location makes a difference in therapy efficacy?
Curr Res Pharmacol Drug Discov. 2022 Mar 19;3:100097. doi: 10.1016/j.crphar.2022.100097. PMID: 35345820; PMCID: PMC8956925.

Yu YQ, Gamez-Belmonte R, Patankar JV, Liebing E, Becker C.
The Role of Programmed Necrosis in Colorectal Cancer.
Cancers (Basel). 2022 Sep 1;14(17):4295. doi: 10.3390/cancers14174295. PMID: 36077828; PMCID: PMC9455009.

Letizia M, Wang YH, Kaufmann U, Gerbeth L, Sand A, Brunkhorst M, Weidner P, Ziegler JF, Böttcher C, Schlickeiser S, Fernández C, Yamashita M, Stauderman K, Sun K, Kunkel D, Prakriya M; IBDome Researchers; Sanders A, Siegmund B, Feske S, Weidinger C.
Store-operated calcium entry controls innate and adaptive immune cell function in inflammatory bowel disease.
EMBO Mol Med. 2022 Sep 7;14(9):e15687. doi: 10.15252/emmm.202215687. Epub 2022 Aug 2. PMID: 35919953; PMCID: PMC9449601.