Hypothesis: Emerging Roles for Aryl Hydrocarbon Receptor in Orchestrating CoV-2-Related Inflammation

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes COVID-19, a multi-organ disease impacting the respiratory system.
• The Aryl hydrocarbon Receptor (AhR) is implicated in inflammatory responses and immune system modulation.
• Understanding AhR's role in COVID-19 pathogenesis is crucial for developing effective treatments.

Purpose of the Study:

• To review mechanisms suggesting AhR's involvement in managing COVID-19's inflammatory framework.
• To explore AhR's regulation of key molecules like ACE-2 and IDO-1.
• To identify AhR as a potential therapeutic target for COVID-19.

Main Methods:

• Literature review of existing data on AhR, COVID-19, and immune responses.
• Analysis of AhR's regulatory functions on ACE-2, B0AT1, and IDO-1.
• Examination of the interplay between AhR, Tryptophan metabolism, and immune cell function.

Main Results:

• AhR regulates Angiotensin Converting Enzyme-2 (ACE-2) and Broad neutral Amino acid Transporter 1 (B0AT1) expression.
• AhR induces Indolamine 2,3 dioxygenase (IDO-1), leading to Tryptophan (Trp) depletion and Kynurenine (Kyn) accumulation, which impairs T cell function.
• AhR and Interferon type I (IFN-I) form an inhibitory loop with NF-kB, limiting innate immunity, while AhR/Kyn binding enhances Interleukin-6 (IL-6) production, promoting inflammation.

Conclusions:

• The Aryl hydrocarbon Receptor (AhR) is intricately involved in the inflammatory processes of COVID-19.
• AhR influences viral entry via ACE-2 regulation and modulates immune responses through Tryptophan metabolism and cytokine production.
• Targeting AhR presents a promising therapeutic avenue for mitigating COVID-19-associated inflammation.