tetano
Editor, Senior Moderator
Lancet Rheumatol
. 2020 Oct 9.
doi: 10.1016/S2665-9913(20)30340-4. Online ahead of print.
Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?
Gaetano Zizzo[SUP] 1 2 [/SUP], Philip L Cohen[SUP] 1 3 [/SUP]
Affiliations
Abstract
The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild-moderate, severe-critical, and chronic-fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33-ST2 axis might act to expand the number of pathogenic granulocyte-macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial-mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.
. 2020 Oct 9.
doi: 10.1016/S2665-9913(20)30340-4. Online ahead of print.
Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?
Gaetano Zizzo[SUP] 1 2 [/SUP], Philip L Cohen[SUP] 1 3 [/SUP]
Affiliations
- PMID: 33073244
- PMCID: PMC7546716
- DOI: 10.1016/S2665-9913(20)30340-4
Abstract
The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild-moderate, severe-critical, and chronic-fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33-ST2 axis might act to expand the number of pathogenic granulocyte-macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial-mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.