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Siebert, K.* ; Faro, T.* ; Köhler, N.* ; Hölz, H.* ; Jarosch, S.* ; Matchado, M.* ; Häcker, D.* ; De Zen, F.* ; Hajji, M.S.* ; Lurz, E.* ; Koletzko, S.* ; Pauling, J.K.* ; Steiger, K.* ; Neuhaus, K.* ; Ohnmacht, C. ; List, M.* ; Busch, D.H.* ; Haller, D.* ; Schwerd, T.*

Endoscopic healing in pediatric IBD perpetuates a persistent signature defined by Th17 cells with molecular and microbial drivers of disease.

Cell Rep. Med. 6:102236 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBDs), mainly achieved by immune-suppressive therapies. However, the chronic and relapsing nature of the disease indicates a lifelong persistence of unknown tissue-associated IBD residues. Based on longitudinally collected gastrointestinal biopsies (n = 217) from pediatric patients with IBD (N = 32) and pediatric non-IBD controls (N = 5), we describe cellular, molecular, and microbial drivers of IBD that persist under EH in the terminal ileum and sigmoid colon. Whole biopsy transcriptomics in combination with single T cell analysis (72,026 cells) characterizes an inflammatory bowel residual disease (IBrD) signature, connecting stress- and inflammation-related tissue markers (e.g., DUOX2, SAA2, and NOS2) with pathogenic interleukin-17 (IL-17)-producing T helper cells. 16S rRNA gene sequencing reveals individual microbial composition with persistently low diversity, irrespective of disease location and activity. Overall, our study identifies a persisting IBD signature that reflects ongoing mucosal alterations despite EH. These markers may provide targets for future or sequential therapies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Duox2 ; Ibd Signature ; Nos2 ; Saa2 ; Th17 ; Bulk Rna ; Endoscopic Healing ; Mucosal 16s Rrna ; Pediatric Ibd ; Single Cell; T-cells; Inflammation; Colitis; Immune; Induction; Chemokine; Balance; Lineage; Alpha
ISSN (print) / ISBN 2666-3791
e-ISSN 2666-3791
Zeitschrift Cell Reports Medicine
Quellenangaben Band: 6, Heft: 7, Seiten: , Artikelnummer: 102236 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Förderungen Bavarian State Ministry of Education and the Arts in the framework of the Bavarian Research Institute for Digital Transformation
Deutsche Forschungsgemeinschaft (DFG
German Research Foundation)
Leona M. and Harry B. Helmsley Charitable Trust
Medical & Clinician Scientist Program (MCSP) of the Faculty of Medicine at LMU Munich
European Research Council (ERC Starting grant)
DFG
European Crohn's and Colitis Organisation (ECCO)