What question did this study set out to answer?

To characterize the role of immune checkpoints in T-cell phenotypes in ulcerative colitis, especially during active disease.

January 23, 2026

P0113Activated PD-1+TIGIT+ T-Cells Define a Tissue-Specific Immune Signature in Active Ulcerative Colitis

Key Points

To characterize the role of immune checkpoints in T-cell phenotypes in ulcerative colitis, especially during active disease.
Collected paired blood and intestinal samples from patients with active and quiescent ulcerative colitis and controls.
Isolated peripheral blood mononuclear cells and lamina propria mononuclear cells.
Used high-dimensional spectral flow cytometry to profile T-cell subsets and activation/checkpoint markers.
Conducted statistical comparisons using Kruskal–Wallis tests.
Identified a unique T-cell subset (PD-1+TIGIT+HLA-DR+CD25+) enriched in the inflamed mucosa of active UC.
Observed depletion of memory T cells in blood, with expansions in the mucosa indicative of active migration.
Noted that this T-cell subset was absent in controls and patients with quiescent UC, emphasizing its specificity to active disease.

Abstract

Abstract Background Immune checkpoints critically regulate T-cell activation and tolerance, yet their role in mucosal immune dysregulation in ulcerative colitis (UC) remains poorly defined. While expansion of regulatory T cells (Treg) in active UC is well-documented, how checkpoints and activation markers shape local T-cell phenotypes remains unclear. Indeed, the paradoxical co-expression of activation and exhaustion markers suggests a complex immune state that may underlie ineffective regulation or persistent inflammation. Characterizing these tissue-specific signatures could reveal biomarkers of disease activity and novel therapeutic targets. Methods Paired blood and intestinal samples were collected from patients with endoscopically active UC (aUC, n = 8), quiescent UC (qUC, n = 5), and non-IBD controls (n = 6). Peripheral blood mononuclear cells (PBMCs) were isolated by ficoll gradient, and lamina propria mononuclear cells (LPMCs) by enzymatic digestion. High-dimensional spectral flow cytometry profiled T-cell subsets and assessed expression of activation (HLA-DR, CD25, CD69) and checkpoint markers (PD-1, CTLA-4, TIGIT, LAG-3, VISTA). Statistical comparisons used Kruskal–Wallis tests with p 0.05 considered significant. Results We uncovered a compartmentalized immune response unique to aUC. In blood, patients showed depletion of memory T cells, Th17, and Treg subsets that were expanded in the inflamed mucosa, consistent with active migration. The mucosal compartment also exhibited a striking enrichment of a PD-1+TIGIT+HLA-DR+CD25+ T-cell subset, completely absent in their circulating precursors or in the blood or mucosa from controls or qUC patients. These cells represented activated/exhausted phenotypes across tissue-resident memory CD8+, effector memory, and pathogenic Th17 subsets. Their expression of both activation markers (HLA-DR, CD25) and inhibitory checkpoints (PD-1, TIGIT) suggest sustained antigenic stimulation and functional exhaustion. The restriction of this population to inflamed tissue indicates local induction by the inflammatory microenvironment and its disappearance during remission highlights a reversible, inflammation-dependent process. Whether these cells represent a failed regulatory mechanism or active drivers of pathology remains to be determined. Conclusion We hereby have identified a unique PD-1+TIGIT+HLA-DR+CD25+ T-cell subset enriched in the inflamed mucosa from aUC but largely absent in remission and controls. This subset may serve as a biomarker of active disease, reflect local immune induction, and illustrate the coexistence of activation and exhaustion that characterizes chronic intestinal inflammation. Conflict of interest: Dr. Romero Castillo, Laura: No conflict of interest Esteva Fernández, Andrea: No conflict of interest López Pascual, Francisco Javier: I declare that I have no conflicts of interest De Prado Santos, Ángel: No conflict of interest. Arribas Rodríguez, Elisa: I have no conflict of interest Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson De Andrés-Asenjo, Beatriz: I have no conflict of interest Godoy Martínez, Lucía: I do not have conflict of interest. Velayos, Benito: No Izquierdo, Sandra: None. Romero, Alejandro: No conflicts Alcaide Suárez, Noelia: No conflicts Cuesta-Sancho, Sara: I have no conflicts of interest to declare Escudero-Hernández, Celia: Grant: ECCO grant, ECCO fellowship Other: ECCO young researcher award 2025, UEG J junior editor Barrio Andres, Jesus: Jesús Barrio has served as a speaker, as consultant or has received research or education funding Abbvie, Takeda,Kern Pharma and Ferring. Fernández-Salazar, Luis: My institution has been granted by Johnosn & Johnson for investigation. I have been financed to attend IBD meetings by Ferring, Lilly and Sandoz. Bernardo, David: David Bernardo has received funding from Pfizer (to develop research projects) as well as from Janssen and Takeda (consulting)

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