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| Item Type: | Article |
|---|---|
| Title: | Epithelial NF-κB shapes protective Treg cell responses to restrain intestinal inflammation |
| Creators: |
Barleben, Luisa  ORCID: https://orcid.org/0000-0002-0400-7117, Schneegans, Antony Julián ORCID: https://orcid.org/0009-0002-6062-7510, Uyar, Bora ORCID: https://orcid.org/0000-0002-3170-4890, Bruneau, Alix ORCID: https://orcid.org/0000-0002-5740-2372, Vasileva, Giomar, Flohr, Franziska, Kabrani, Eleni ORCID: https://orcid.org/0000-0003-0834-9912, Vasilakis, Thomas, Hammann, Linda, Gebert, Pimrapat ORCID: https://orcid.org/0000-0002-5946-7137, Dietrich, Carola, Bochow-Fitzner, Bettina, Arnold, Alexander, Sai, Somesh ORCID: https://orcid.org/0000-0001-6865-341X, Gröne, Florentine, Sander, Maike ORCID: https://orcid.org/0000-0001-5308-7785, Conrad, Thomas ORCID: https://orcid.org/0000-0001-5618-6295, Gérard, Audrey ORCID: https://orcid.org/0000-0003-3059-3065, Piseddu, Ignazio, Anz, David, Jochum, Christoph, Akalin, Altuna ORCID: https://orcid.org/0000-0002-0468-0117, Hammerich, Linda ORCID: https://orcid.org/0000-0003-0557-3927, Klose, Christoph S.N. ORCID: https://orcid.org/0000-0001-8803-2979, Tacke, Frank ORCID: https://orcid.org/0000-0001-6206-0226, Di Virgilio, Michela ORCID: https://orcid.org/0000-0001-5189-0793 and Kolesnichenko, Marina ORCID: https://orcid.org/0000-0001-7366-9061
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| Abstract: | Inflammation resolution depends on coordinated communication between tissue compartments, yet how the intestinal epithelium shapes its immune microenvironment remains poorly understood. Here, using colonic biopsies from patients with ulcerative colitis (UC) and mouse models enabling tissue-wide visualization of NF-κB activity, we combine single-cell RNA sequencing and secretome analysis to define epithelial communication during colitis. We show that, paradoxically, the NF-κB-driven pro-inflammatory secretome of intestinal epithelial cells (IECs) is essential for recovery and prevents unrestrained inflammation. Mechanistically, epithelial NF-κB promotes CCL22-dependent regulatory T cell (Treg cell) recruitment and promotes a tolerogenic, pro-repair cell state, accompanied by induction of the lipid-metabolism-associated GDPD3 and CCR4. In UC, epithelial NF-κB is not uniformly activated but instead induces a selective pro-inflammatory transcriptional program while repressing targets regulating T cell recruitment. Thus, we identify dynamic epithelial-immune communication and demonstrate a protective IEC NF-κB-Treg cell axis important for resolution of intestinal inflammation. |
| Keywords: | Animal Disease Models, Chemokine CCL22, Colon, Epithelial Cells, Inbred C57BL Mice, Inflammation, Intestinal Mucosa, NF-kappa B, Regulatory T-Lymphocytes, Ulcerative Colitis, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 17 |
| Number: | 1 |
| Page Range: | 10956 |
| Date: | 20 October 2026 |
| Official Publication: | https://doi.org/10.1038/s41467-026-78796-z |
| PubMed: | View item in PubMed |
| Related to: |
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