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Reduced frequency of circulating regulatory T cells and their related immunosuppressive mediators in treated celiac patients

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Abstract

Background

Regulatory T cells (Tregs) have an important role in the control of the immune responses. This study aimed to compare the frequency of peripheral blood (PB) CD4+ CD25+ FoxP3+ Treg cells and PB and duodenal expression levels of pro- and anti-inflammatory mediators in treated celiac disease (CD) patients and healthy controls.

Methods and results

Duodenal biopsy specimens and PB samples were collected from 60 treated CD patients and 60 controls. Flow cytometry analysis was conducted on peripheral blood mononuclear cell (PBMC) specimens and relative PB and duodenal mRNA expression levels of CD25, forkhead box P3 (Foxp3), interleukin (IL)-10 and granzyme B (GrzB) were evaluated using quantitative real-time PCR. The levels of serum IL-10 and IL-6 were tested with sandwich enzyme-linked immunosorbent assay kits. p values < 0.05 were considered significant. Flow cytometry analysis showed a significant decrease in the number of Tregs in CD patients’ PBMC specimens (p = 0.012). CD25 and Foxp3 PB mRNA expressions were also lower in CD patients without reaching the significance level (p > 0.05). IL-10 PB mRNA and protein expression did not differ between the groups (p > 0.05), and GrzB PB expression was significantly reduced in CD patients (p = 0.001). In duodenal specimens of CD patients, while significantly increased CD25, Foxp3 mRNA expression (p = 0.01 and 0.001, respectively) and decreased IL-10 mRNA expression (p = 0.02) were observed, GrzB mRNA expression did not differ between groups (p > 0.05). Moreover, a high serum level of IL-6 was observed in CD patients (p = 0.001).

Conclusions

Despite following the gluten free diet, there may still be residual inflammation in the intestine of CD patients. Accordingly, finding a therapeutic approach based on strengthening the function of Treg cells in CD might be helpful.

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Acknowledgements

The authors would like to acknowledge the Gastroenterology and Liver Diseases Research Center of Shahid Beheshti University of Medical Sciences for their support and contribution to this study. The authors would also like to thanks Dr Robert P Anderson from Wesley Medical Research—The Wesley Hospital, Brisbane, Queensland, Australia for his critical review.

Funding

Research reported in this publication was supported by Elite Researcher Grant Committee under Award Number (983076) from the National Institute for Medical Research Development (NIMAD), Tehran, Iran and Gastroenterology and Liver Diseases Research Center of Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nastaran Asri

  2. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Rostami-Nejad, Elham Aghamohamadi, Hamid Asadzadeh-Aghdaei & Mohammad Reza Zali

  3. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abdolrahim Nikzamir

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  4. Elham Aghamohamadi
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Contributions

Design of experiments by MRN and AN. Analysis of data by NA and EA. First draft of manuscript by NA, and subsequent drafting by MRN, MRZ and HAA. All authors read and approved the final manuscript.

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Correspondence to Mohammad Rostami-Nejad.

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The authors have no relevant financial or non-financial interest to disclose.

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The study was approved by the ethical committee of the Research Institute for Gastroenterology and Liver Diseases (RIGLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran (IR.SBMU.MSP.REC.1397.564).

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Asri, N., Rostami-Nejad, M., Nikzamir, A. et al. Reduced frequency of circulating regulatory T cells and their related immunosuppressive mediators in treated celiac patients. Mol Biol Rep 49, 8527–8535 (2022). https://doi.org/10.1007/s11033-022-07674-w

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  • DOI: https://doi.org/10.1007/s11033-022-07674-w

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