Aryl hydrocarbon receptor role in co-ordinating sars-cov-2 entry and symptomatology: Linking cytotoxicity changes in covid-19 and cancers; modulation by racial discrimination stress

Research output: Contribution to journalArticlepeer-review

Abstract

There is an under-recognized role of the aryl hydrocarbon receptor (AhR) in co-ordinating the entry and pathophysiology of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that underpins the COVID-19 pandemic. The rise in pro-inflammatory cytokines during the ‘cytokine storm’ induce indoleamine 2,3-dioxygenase (IDO), leading to an increase in kynurenine that activates the AhR, thereby heightening the initial pro-inflammatory cytokine phase and suppressing the endogenous anti-viral response. Such AhR-driven changes underpin the heightened severity and fatality associated with pre-existent high-risk medical conditions, such as type II diabetes, as well as to how racial discrimination stress contributes to the raised severity/fatality in people from the Black Asian and Minority Ethnic (BAME) communities. The AhR is pivotal in modulating mitochondrial metabolism and co-ordinating specialized, pro-resolving mediators (SPMs), the melatonergic pathways, acetyl-coenzyme A, and the cyclooxygenase (COX) 2-prostaglandin (PG) E2 pathway that underpin ‘exhaustion’ in the endogenous anti-viral cells, paralleling similar metabolic suppression in cytolytic immune cells that is evident across all cancers. The pro-inflammatory cytokine induced gut permeability/dysbiosis and suppression of pineal melatonin are aspects of the wider pathophysiological underpinnings regulated by the AhR. This has a number of prophylactic and treatment implications for SARS-CoV-2 infection and cancers and future research directions that better investigate the biological underpinnings of social processes and how these may drive health disparities.

Original languageEnglish
Article number249
Pages (from-to)1-31
Number of pages31
JournalBiology
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Acetyl-CoA
  • Aryl hydrocarbon receptor
  • Cancer
  • COVID-19
  • Immune
  • Melatonin
  • Mitochondria
  • Racism
  • SARS-CoV-2
  • Treatment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Aryl hydrocarbon receptor role in co-ordinating sars-cov-2 entry and symptomatology: Linking cytotoxicity changes in covid-19 and cancers; modulation by racial discrimination stress'. Together they form a unique fingerprint.

Cite this