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Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis
Lena S Mayer1,2, Jakob Arnold1,3, Felix Roettele1,3
1Department of Medicine II (Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Science Immunology
|February 6, 2026
Summary
Gamma delta (γδ) T cells play a role in ulcerative colitis (UC) pathogenesis. Specific γδ T cell subsets shift during UC, impacting intestinal immunity and potentially offering therapeutic targets.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Gamma delta (γδ) T cells are crucial for maintaining intestinal immune homeostasis.
- Their specific roles and alterations in human ulcerative colitis (UC) remain unclear.
Purpose of the Study:
- To characterize γδ T cell populations in the intestines of UC patients.
- To understand the functional phenotypes and distribution of γδ T cells in UC.
- To explore the relationship between γδ T cells and epithelial cells in UC.
Main Methods:
- Single-cell RNA sequencing of intestinal biopsies.
- T cell receptor (TCR) profiling.
- Mass cytometry analysis.
Main Results:
- UC is associated with a decrease in CD103+Vγ4Vδ1+ γδ T cells in the intraepithelial compartment.
- Expansion of stem-like (TCF-1+, PD-1+) and effector-like (granzyme B+, perforin+, T-bet+) γδ T cell subsets in the lamina propria of UC patients.
- Changes in γδ T cell composition correlate with altered expression of butyrophilin (BTN) genes in epithelial cells.
- Peripheral blood γδ T cells also show inflammation-associated alterations.
- Clinical improvement in UC patients led to recovery of γδ T cells and reduced inflammation.
Conclusions:
- Distinct γδ T cell subsets exhibit both protective and pathogenic functions in UC.
- Alterations in γδ T cell populations are linked to disease activity and epithelial cell interactions.
- γδ T cells represent potential biomarkers and therapeutic targets for UC.
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