Case Control Study
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World J Gastroenterol. Mar 28, 2025; 31(12): 97120
Published online Mar 28, 2025. doi: 10.3748/wjg.v31.i12.97120
Decreased gene expression of interleukin 2 receptor subunit γ (CD132) in tissues of patients with Crohn’s disease
Juan Carlos Andreu-Ballester, Carolina Hurtado-Marcos, Carlos García-Ballesteros, Jaime Pérez-Griera, Fernando Izquierdo, Dolores Ollero, Ana Jiménez, Rafael Gil-Borrás, Antonio Llombart-Cussac, Francisca López-Chuliá, Carmen Cuéllar
Juan Carlos Andreu-Ballester, Department of Research, Fisabio Foundation, Valencia 46020, Spain
Juan Carlos Andreu-Ballester, Carmen Cuéllar, Parasitic Immunobiology and Immunomodulation Research Group, Complutense University, Madrid 28040, Spain
Carolina Hurtado-Marcos, Fernando Izquierdo, Dolores Ollero, Laboratory of Parasitology, San Pablo-CEU University, Boadilla del Monte, Madrid 28660, Spain
Carlos García-Ballesteros, Francisca López-Chuliá, Department of Hematology, Arnau de Vilanova Hospital, Valencia 46020, Spain
Jaime Pérez-Griera, Department of Biopathology, Hospital Clinico Universitario, Valencia 46010, Spain
Ana Jiménez, Department of Pathology, Arnau de Vilanova Hospital, Valencia 46020, Spain
Rafael Gil-Borrás, Department of Digestive, Lluis Alcanyis Hospital of Xàtiva, Jativa, Valencia 46800, Spain
Antonio Llombart-Cussac, Department of Medical Oncology, Oncology Department, Valencia 46020, Spain
Francisca López-Chuliá, Department of Medicine, Cardenal Herrera University, Valencia 46115, Spain
Carmen Cuéllar, Department of Microbiology and Parasitology, Complutense University, Madrid 28040, Spain
Author contributions: Andreu-Ballester JC, Hurtado-Marcos C, and Cuéllar C contributed to the conception and design of the work; Gil-Borrás R contributed to the data collection and recruitment of patients; García-Ballesteros C and López-Chuliá F contributed to the flow cytometry analysis of T cell subsets and apoptosis; Pérez-Griera J and Cuéllar C contributed to interleukin 7 analysis and preparation of tissues for cytometry analysis; Hurtado-Marcos C, Ollero D and Izquierdo F contributed to PCR analysis of gene expression in tissues; Jiménez A contributed to tissue sampling; Andreu-Ballester JC contributed to the statistical method; Andreu-Ballester JC, Hurtado-Marcos C and Cuéllar C contributed to the interpretation of data for this work; Andreu-Ballester JC, Hurtado-Marcos C, Llombart-Cussac A, and Cuéllar C contributed to the final approval of the version to be submitted.
Institutional review board statement: This study was conducted following the recommendations of the Spanish Bioethics Committee, the Spanish legislation on Biomedical Research (Law 14/2007) and Personal Data Protection (Spanish Law 3/2018 and European Law UE676/2018). The anonymity of the subjects participating in the study has been ensured. The study was approved by the Ethics and Investigation Committee of the Arnau de Vilanova-Lliria University Hospital (Valencia, Spain).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: No additional data is available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Juan Carlos Andreu-Ballester, MD, PhD, Researcher, Department of Research, Fisabio Foundation, Av de Cataluña 21, Valencia 46020, Spain. jcandreuballester@outlook.com
Received: May 23, 2024
Revised: September 20, 2024
Accepted: October 25, 2024
Published online: March 28, 2025
Processing time: 306 Days and 23.7 Hours
Abstract
BACKGROUND

A deficiency of γδ T cells has been described in Crohn's disease (CD).

AIM

To analyze the gene expression of interleukin 7 (IL-7) and its receptors in the tissues of patients with CD.

METHODS

We studied the peripheral blood of 80 patients with CD, comparing them with a group of 80 healthy subjects. The number and apoptosis of αβ and γδ T cells in peripheral blood and the proportion of αβ and γδ T cells in the intestinal tissues of patients with CD (n = 25) were studied. The gene and protein expression of IL-7, IL-2 receptor subunit γ [cluster of differentiation 132 (CD132)], receptor α (CD127), and caspase-3 in tissues was analyzed by quantitative PCR. Serum IL-7 levels were also analyzed.

RESULTS

In patients with CD, a decreased number of γδ T cells and an increase in the apoptosis of CD56+ αβ and γδ T cells in peripheral blood was observed (P < 0.0001 and P < 0.01) respectively, and there was an inverse correlation among T subsets and their apoptosis. In addition, IL-7 gene expression and IL-7 protein in the tissues of these patients were increased. The titers of caspase-3 in tissues were low vs control group (P > 0.01). The percentage of CD8+γδ T cells decreased in tissues (P < 0.01), and was directly related to IL-7 levels in peripheral blood. The expression of IL-2 receptor subunit γ (CD132) was greatly decreased in the tissues of patients with CD (P < 0.05).

CONCLUSION

There may be a cause-effect relationship between the lower gene expression of the IL-2 receptor subunit γ (CD132) in tissues of patients with CD and γδ T cells immunodeficiency.

Keywords: Crohn’s disease; Interleukin 7; Interleukin 2 receptor subunit γ (CD 132); Caspase-3; γδ T cells

Core Tip: A deficiency in T cells, and specifically in γδ T cells, has been described in Crohn's disease (CD). Interleukin 7 (IL-7) is essential for the activation and proliferation of this lymphocyte’s subsets. This work demonstrates a decrease in IL-2 receptor subunit γ [cluster of differentiation 132 (CD132)] in tissues of patients with CD. This could be related to the deficiency of γδ T cells, and could open new works and lines of research for the application of new therapies against this disease.