A05

Oncostatin M as a modulator of pathogenic memory T cells in IBD

A05

Project Summary

Oncostatin M (OSM) is a highly expressed cytokine in IBD, and elevated OSM levels prior to treatment are strongly associated with failure of anti-TNF-α therapy. OSM promotes intestinal inflammatory pathology, and both genetic deletion and pharmacological blockade of OSM significantly reduce colitis in mouse models. We hypothesize that OSM acts as an amplifier of inflammation and a driver of disease chronicity by targeting both stromal and epithelial cells. We believe that a deeper understanding of the OSM–OSMR signaling pathway in intestinal biology may support the development of novel therapeutic strategies targeting this pathway in inflammatory bowel diseases.

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.

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.

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.

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.

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.

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.

Atreya I, Neurath MF.
Linking IL-10 signaling with lipid metabolic programs in macrophages: dysregulated ceramide homeostasis drives colitis.
Signal Transduct Target Ther. 2024 Jun 8;9(1):156. doi: 10.1038/s41392-024-01864-7. PMID: 38851767; PMCID: PMC11162417.
Projekte: A07, C04

Hegazy AN, Peine C, Niesen D, Panse I, Vainshtein Y, Kommer C, Zhang Q, Brunner TM, Peine M, Fröhlich A, Ishaque N, Marek RM, Zhu J, Höfer T, Löhning M.
Plasticity and lineage commitment of individual TH1 cells are determined by stable T-bet expression quantities.
Sci Adv. 2024 Jun 7;10(23):eadk2693. doi: 10.1126/sciadv.adk2693. Epub 2024 Jun 5. PMID: 38838155; PMCID: PMC11152138.

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.

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.