Academic Journal
Mucosal regulatory and effector T-cell imbalance in CVID-associated enteropathy.
| Title: | Mucosal regulatory and effector T-cell imbalance in CVID-associated enteropathy. |
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| Authors: | Demir S; Division of Immunology and Allergy Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Kahveci N; Division of Immunology and Allergy Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Gelmez MY; Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye., Unal D; Division of Immunology and Allergy Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Yegit OO; Division of Immunology and Allergy Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Yagli MA; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., İstemihan Z; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Berker N; Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Cavus B; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Besisik F; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Cetin Aktas E; Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye., Gelincik A; Division of Immunology and Allergy Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye., Deniz G; Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye. |
| Source: | Frontiers in immunology [Front Immunol] 2026 Sep 03; Vol. 17, pp. 1937502. Date of Electronic Publication: 2026 Sep 03 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | Common Variable Immunodeficiency*/immunology , Common Variable Immunodeficiency*/complications , T-Lymphocytes, Regulatory*/immunology , T-Lymphocytes, Regulatory*/metabolism , Intestinal Mucosa*/immunology , Intestinal Mucosa*/pathology , Intestinal Mucosa*/metabolism , T-Lymphocyte Subsets*/immunology , T-Lymphocyte Subsets*/metabolism , Intestinal Diseases*/immunology , Intestinal Diseases*/etiology, Duodenum/immunology ; Duodenum/pathology ; Cytokines/metabolism ; Ileum/immunology ; Ileum/pathology ; Humans ; Female ; Male ; Adult ; Middle Aged ; Young Adult ; Immunity, Mucosal |
| 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 γδ T cells and a trend toward reduced Treg frequencies. Intracellular IL-17 production was markedly decreased in both mucosal and γδ T cell subsets. In the ileum, EP patients displayed reduced Treg frequencies together with increased γδ T cells and enhanced IFN-γ production by γδ 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 γδ T cell expansion in the duodenum, together with reduced Treg frequencies and increased IFN-γ-producing γδ 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. (Copyright © 2026 Demir, Kahveci, Gelmez, Unal, Yegit, Yagli, İstemihan, Berker, Cavus, Besisik, Cetin Aktas, Gelincik and Deniz.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: T cell; T cell subgroup; Treg - regulatory T cell; common variable immune deficiency (CVID); effector T cell; enteropathy; intestinal T cells; mucosal immunity |
| Substance Nomenclature: | 0 (Cytokines) |
| Entry Date(s): | Date Created: 20260918 Date Completed: 20260918 Latest Revision: 20260919 |
| Update Code: | 20260919 |
| PubMed Central ID: | PMC13582527 |
| DOI: | 10.3389/fimmu.2026.1937502 |
| PMID: | 42756343 |
| Database: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1937502 |