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. 2025 Jul;33(7):4115-4124.
doi: 10.1007/s10787-025-01828-5. Epub 2025 Jul 1.

Aryl-hydrocarbon receptor dysregulation and its correlation with immunomodulatory markers in COVID-19 patients

Abeda Mazari #  1   2 , Mohammad Hossein Nicknam #  1   2 , Sara Assadiasl  1 , Maryam Sadr  1 , Hanieh Mojtahedi  1 , Maryam Ahmadi  2 , Sina Enayat  1   3 , Alireza Asgari  4 , Narjes Soleimanifar  5
Affiliations

Aryl-hydrocarbon receptor dysregulation and its correlation with immunomodulatory markers in COVID-19 patients

Abeda Mazari et al. Inflammopharmacology. 2025 Jul.

Abstract

Introduction: The COVID-19 pandemic with various clinical symptoms has posed significant challenges to the healthcare system. The aryl-hydrocarbon receptor (AhR), a transcription factor that can be activated by both external and internal ligands, may play a role in the regulation of pro-inflammatory cytokines, including interleukin (IL)-6. Additionally, indoleamine-2,3-dioxygenase (IDO)-1 is thought to have an immunomodulatory role and provides kynurenine, an AhR agonist. This research aimed to examine the alteration of AhR and IDO-1 gene expression in patients diagnosed with COVID-19 as well as evaluate their correlation with IL-6 and interferon (IFN)-α serum levels.

Methods: A total of 30 patients diagnosed with COVID-19, along with 30 healthy individuals matched for age and gender, were chosen to serve as the control group. The gene expressions of AhR and IDO-1 were assessed using RT-PCR as well as the serum concentration of IL-6 was measured using ELISA techniques.

Results: The results showed an increased level of AhR gene expression (p value: 0.017), and elevated serum levels of IL-6 (p value: 0.044) in the patients with COVID analyzed alongside the control group. However, IDO-1 gene expression was slightly downregulated. IFN-α serum levels were comparable between the two groups. AhR gene expression had a weak negative correlation with IDO-1 expression. Neither IL-6 nor IFN-α showed a correlation with AhR expression; nonetheless, IL-6 demonstrated an increasing pattern by disease severity.

Conclusion: This study's outcomes revealed a dysregulated expression of AhR and IDO-1 in COVID-19 patients. IL-6 was elevated, but IDO-1 as an immunomodulatory molecule was suppressed. Besides, AhR expression showed no correlation with IDO-1, IL-6, or IFN-α levels.

Keywords: Aryl hydrocarbon receptor; COVID-19; Indoleamin2,3-dioxygenase-1; Interferon-alpha; Interleukin-6.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Ethical approval: All the techniques carried out in the present study involving human participants were in accordance with the standards of the institutional research committee and with the Helsinki declaration and its later amendments or comparable ethical standards. It has ethical approval of Tehran University of medical sciences (Code: IR.TUMS.CHMC.REC.1401.131). Informed consent was obtained from all participants after describing the process and goals of the study.

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