Heightened expression of CD39 by regulatory T lymphocytes is associated with therapeutic remission in inflammatory bowel disease
Open accessAbstract
BACKGROUND: To evaluate whether changes in expression of CD39 by regulatory T lymphocytes (Treg) impact treatment response in inflammatory bowel disease. To then define the biological role of expression of CD39 on Treg in an animal model of colitis. METHODS: A prospective study of consecutive patients commencing anti-tumor necrosis factor therapy with infliximab (IFX) or adalimumab (ADA), who were then followed for 12 months. Treatment responses were defined both symptomatically and by endoscopy showing mucosal healing. Peripheral blood Tregs were quantified by flow cytometry. Functional importance of CD39 expression by Treg was determined in an adoptive T-cell transfer model of colitis. RESULTS: Forty-seven patients (ulcerative colitis, n = 22; Crohn's disease, n = 25) were recruited; 16 patients were complete responders and 13 nonresponders to anti-tumor necrosis factor. CD39 expression by Treg was lower in active inflammatory bowel disease and increased significantly after treatment in responders (CD39Treg/total Treg; 8% at baseline to 22.5% at late time point, P < 0.001). Responders were more likely to have therapeutic drug levels and in multivariate analysis therapeutic drug levels were associated with higher expression of CD39 by FoxP3 Treg and lower frequencies of interleukin 17A expressing cells. Tregs with genetic deletion of CD39 exhibit decrements in potential to suppress intestinal inflammation in a murine (CD45RB) T-cell transfer model of colitis in vivo, when compared with wild-type Treg. CONCLUSIONS: Increased expression of CD39 by peripheral blood Treg is observed in the setting of clinical and endoscopic remission in inflammatory bowel disease. Deficiency of CD39 expression by Treg can be linked to inability to suppress experimental colitis.
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An increase in ENTPD1 expression on peripheral-blood Tregs is associated with remission of IBD.
“an increase in ENTPD1 expression on peripheral-blood Tregs has been associated with remission of IBD (Gibson et al., 2015).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Gibson et al., 2015
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Valdez-Moráles, E. E., Liñán-Rico, A., & Alba, R. G. (2026) · Frontiers in Gastroenterology · doi:10.3389/fgstr.2026.1954794
- Authors
- Gibson, D. J., Elliott, L., McDermott, E., Tosetto, M., Keegan, D., Byrne, K., Martin, S. T., Rispens, T., Cullen, G., Mulcahy, H. E., Cheifetz, A. S., Moss, A. C., Robson, S. C., Doherty, G. A., & Ryan, E. J.
- Affiliations
- University College Dublin (IE)
- Amsterdam UMC Location University of Amsterdam (NL)
- ORCID
- Venue
- Inflammatory Bowel Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-12
- Volume
- 21
- Issue
- 12
- Pages
- 2806-2814
- ISSN
- 1078-0998 (ISSN-L)
- OpenAlex
- W2413587463
- Cited by
- 62
- References
- 26
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 6
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Inflammatory Bowel Diseases (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- UCD Foundation
- National Heart, Lung, and Blood Institute (R01HL094400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- CD39, regulatory T cells
- MeSH terms
- Adalimumab, Infliximab, Adult, Animals, Anti-Inflammatory Agents, Antibodies, Monoclonal, Apyrase, Colitis, Ulcerative, Crohn Disease, Female, Gastrointestinal Agents, Humans, Immunologic Factors, Male, Middle Aged, Prospective Studies, Remission Induction, Tumor Necrosis Factor-alpha, Antigens, CD, Interleukin-17, T-Lymphocytes, Regulatory, Mice, Young Adult
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