Mucosal regulatory and effector T-cell imbalance in CVID-associated enteropathy
FRONTIERS IN IMMUNOLOGY, vol.17, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 17
- Publication Date: 2026
- Doi Number: 10.3389/fimmu.2026.1937502
- Journal Name: FRONTIERS IN IMMUNOLOGY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
- Open Archive Collection: AVESIS Open Access Collection
- Istanbul University Affiliated: Yes
Abstract
Background Common variable immunodeficiency (CVID) frequently presents with gastrointestinal complications, yet the immunopathogenesis of CVID-associated enteropathy remains poorly understood.Objective This study aimed to investigate intestinal T cell subset distributions and intracellular cytokine profiles in order to better understand mucosal immune alterations associated with enteropathy in CVID.Methods Duodenal and ileal biopsy specimens were obtained from CVID patients with enteropathy (EP, n=11) and without enteropathy (EN, n=13), patients with Crohn's disease (CD, n=9), and healthy controls (HC, n=14). Lamina propria mononuclear cells were isolated and analyzed by flow cytometry to determine T-cell phenotypes, maturation status, and intracellular cytokine production following stimulation.Results Duodenal tissue from EP patients showed significantly reduced frequencies of total T, cytotoxic T, mucosal T, mucosal cytotoxic T, accompanied by an expansion of gamma delta T cells and a trend toward reduced Treg frequencies. Intracellular IL-17 production was markedly decreased in both mucosal and gamma delta T cell subsets. In the ileum, EP patients displayed reduced Treg frequencies together with increased gamma delta T cells and enhanced IFN-gamma production by gamma delta T cells.Conclusions This study identifies distinct, compartment-specific alterations in duodenal and ileal T cell profiles in CVID-associated enteropathy. Reduced IL-17 production and gamma delta T cell expansion in the duodenum, together with reduced Treg frequencies and increased IFN-gamma-producing gamma delta T cells in the ileum, characterized CVID-associated enteropathy. These findings indicate disrupted mucosal immune homeostasis and provide a basis for future longitudinal and mechanistic studies.