TNF signaling drives expansion of Reg4+ epithelial cells in colitis.
Gadeock, S.; Girish, N.; Liu, C. Y.; Huang, Y.; Grikscheit, T. C.; Polk, D. B.
Show abstract
Reg4+ secretory cells are upregulated in colitis and promote epithelial repair, but their regulation is poorly understood. We show that TNF-TNFR1 signaling controls Reg4+ cell numbers in mouse and human colonoids and in vivo, with TNFR1 deficiency reducing these cells and TNF restoring them dose-dependently. In UC patients and DSS-colitis, REG4+ cells mark regenerating crypts, and persistent REG4, DUOX2, and TNFR1 expression identifies non-responders to anti-TNF therapy. These findings reveal a TNFR1-dependent mechanism regulating Reg4+ cells and suggest potential strategies to improve therapeutic responses in IBD.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Reduced intestinal GLP-1+ cell numbers are associated with an inflammation-related epithelial metabolic signature 97%
- An epigenetic basis for sustained inflammatory epithelial progenitor cell states in Crohn's disease 95%
- Histopathologic Evaluation and Single-Cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients with Inflammatory Bowel Disease. 95%
Similar papers in this journal
- SMAD4 suppresses colitis-associated carcinoma through inhibition of CCL20/CCR6-mediated inflammation 96%
- Transcriptional Atlas of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis Patients 95%
- Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness 95%
Similar papers in this journal
- Epithelial HO-1 regulates iron availability and promotes colonic tumorigenesis in a context-dependent manner 95%
- The Septin Cytoskeleton is a Novel Regulator of Intestinal Epithelial Barrier Integrity and Mucosal Inflammation 95%
- MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn's disease 95%
Similar papers in this journal
- Inflammation induced Th17 cells synergize with the inflammation-trained microbiota to mediate host-resiliency against intestinal injury 95%
- M1 and M2 macrophages differentially regulate colonic crypt renewal. 92%
- The G-protein coupled receptor OXER1 is a tissue redox sensor essential for intestinal epithelial barrier integrity. 92%
Similar papers in this journal
- A20's Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis 96%
- Microbial signals and lymphotoxin drive TNF-independent death of A20 and ABIN-1 deficient epithelium 96%
- Intestinal epithelial MHC class II regulation by HDAC3 instructs microbiota-specific CD4+ T cells 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.