Impact of epithelial dysfunction on neuroimmune crosstalk in IBD
Project Summary
At the intestinal mucosa, the interplay between the commensal microbiota, the epithelium, and the immune system is essential for maintaining homeostasis. Disruptions in this balance can lead to chronic inflammation. The gut harbors its own intrinsic nervous system—the enteric nervous system (ENS). While various findings suggest that the ENS plays an important role in chronic intestinal inflammation, its precise function in this context remains poorly understood. In this project, we investigate how the ENS interacts with key components of mucosal homeostasis to regulate chronic inflammation. Our data indicate that enteric neurons mount a conserved response to diverse inflammatory stimuli by sensing inflammatory mediators such as interferons. Our research program focuses on how inflammation alters the function of enteric neurons and how the ENS contributes to intestinal homeostasis.
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.
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.
Feng X, Andersson T, Flüchter P, Gschwend J, Berest I, Muff JL, Lechner A, Gondrand A, Westermann P, Brander N, Carchidi D, De Tenorio JC, Pan T, Boehm U, Klose CSN, Artis D, Messner CB, Leinders-Zufall T, Zufall F, Schneider C.
Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation.
Nat Immunol. 2025 Apr;26(4):567-581. doi: 10.1038/s41590-025-02104-y.
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.
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.
Erkert L, Ruder B, Kabisch M, Gamez Belmonte R, Patankar JV, Gonzalez Acera M, Schödel L, Chiriac MT, Cineus R, Gnafakis S, Leupold T, Thoma OM, Stolzer I, Taut A, Thonn V, Zundler S, Günther C, Diefenbach A, Kühl AA, Hegazy AN, Waldner M, Basic M, Bleich A, Neurath MF, Wirtz S, Becker C; TRR241 IBDome Consortium.
TIFA renders intestinal epithelial cells responsive to microbial ADP-heptose and drives colonic inflammation in mice.
Mucosal Immunol. 2025 Apr;18(2):453-466. doi: 10.1016/j.mucimm.2025.01.003.
Forster PM, Jakob MO, Yusuf D, Bubeck M, Limberger H, Luo Y, Thieme P, Polici A, Sterczyk N, Boulekou S, Bartel L, Cosovanu C, Witkowski M, González-Acera M, Kühl AA, Weidinger C; TRR241 IBDome Consortium; Backofen R, Hegazy AN, Patankar JV, Klose CSN.
A transcriptional atlas of gut-innervating neurons reveals activation of interferon signaling and ferroptosis during intestinal inflammation.
Neuron. 2025 May 7;113(9):1333-1351.e7. doi: 10.1016/j.neuron.2025.02.018.
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.
Troch KF, Jakob MO, Forster PM, Jarick KJ, Schreiber J, Preusser A, Guerra GM, Durek P, Tizian C, Sterczyk N, Helfrich S, Duerr CU, Voehringer D, Witkowski M, Artis D, Rollenske T, Kruglov AA, Mashreghi MF, Klose CSN.
Group 2 innate lymphoid cells are a non-redundant source of interleukin-5 required for development and function of murine B1 cells.
Nat Commun. 2024 Dec 4;15(1):10566. doi: 10.1038/s41467-024-54780-3. PMID: 39632879; PMCID: PMC11618303.
Topczewska PM, Savvopoulou A, Cosovanu C, Klose CSN.
Transcriptional profiling identifies IL-33-expressing intestinal stromal cells as a signaling hub poised to interact with enteric neurons.
Front Cell Dev Biol. 2024 Aug 1;12:1420313. doi: 10.3389/fcell.2024.1420313. PMID: 39149516; PMCID: PMC11325031.
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.
Gámez-Belmonte R, Wagner Y, Mahapatro M, Wang R, Erkert L, González-Acera M, Cineus R, Hainbuch S, Patankar JV, Voehringer D, Hegazy AN, Neurath MF, Wirtz S, Becker C.
Intestinal epithelial Gasdermin C is induced by IL-4R/STAT6 signaling but is dispensable for gut immune homeostasis.
Sci Rep. 2024 Nov 3;14(1):26522. doi: 10.1038/s41598-024-78336-z. PMID: 39489845; PMCID: PMC11532336.
Erkert L, Gamez-Belmonte R, Kabisch M, Schödel L, Patankar JV, Gonzalez-Acera M, Mahapatro M, Bao LL, Plattner C, Kühl AA, Shen J, Serneels L, De Strooper B; TRR241 IBDome Consortium; Neurath MF, Wirtz S, Becker C.
Alzheimer’s disease-related presenilins are key to intestinal epithelial cell function and gut immune homoeostasis.
Gut. 2024 Sep 9;73(10):1618-1631. doi: 10.1136/gutjnl-2023-331622. PMID: 38684238.
Röwekamp I, Maschirow L, Rabes A, Fiocca Vernengo F, Hamann L, Heinz GA, Mashreghi MF, Caesar S, Milek M, Fagundes Fonseca AC, Wienhold SM, Nouailles G, Yao L, Mousavi S, Bruder D, Boehme JD, Puzianowska-Kuznicka M, Beule D, Witzenrath M; CAPNETZ Study Group; Löhning M, Klose CSN, Heimesaat MM, Diefenbach A, Opitz B.
IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota.
Proc Natl Acad Sci U S A. 2024 May 28;121(22):e2310864121. doi: 10.1073/pnas.2310864121. Epub 2024 May 23. PMID: 38781213; PMCID: PMC11145264.
Gamez-Belmonte R, Mahapatro M, Erkert L, Gonzalez-Acera M, Naschberger E, Yu Y, Tena-Garitaonaindia M, Patankar JV, Wagner Y, Podstawa E, Schödel L, Bubeck M, Neurath MF, Stürzl M, Becker C.
Epithelial presenilin-1 drives colorectal tumour growth by controlling EGFR-COX2 signalling.
Gut. 2023 Jun;72(6):1155-1166. doi: 10.1136/gutjnl-2022-327323. Epub 2022 Oct 19. PMID: 36261293.
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.
Jarick KJ, Topczewska PM, Jakob MO, Yano H, Arifuzzaman M, Gao X, Boulekou S, Stokic-Trtica V, Leclère PS, Preußer A, Rompe ZA, Stamm A, Tsou AM, Chu C, Heinrich FR, Guerra GM, Durek P, Ivanov A, Beule D, Helfrich S, Duerr CU, Kühl AA, Stehle C, Romagnani C, Mashreghi MF, Diefenbach A, Artis D, Klose CSN.
Non-redundant functions of group 2 innate lymphoid cells.
Nature. 2022 Nov;611(7937):794-800. doi: 10.1038/s41586-022-05395-5. Epub 2022 Nov 2. PMID: 36323785; PMCID: PMC7614745.
Yu YQ, Thonn V, Patankar JV, Thoma OM, Waldner M, Zielinska M, Bao LL, Gonzalez-Acera M, Wallmüller S, Engel FB, Stürzl M, Neurath MF, Liebing E, Becker C.
SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth.
Cell Death Dis. 2022 Jan 12;13(1):52. doi: 10.1038/s41419-021-04483-0. PMID: 35022391; PMCID: PMC8755774.