The Role of Interleukin-33 in Organ Fibrosis

TY - JOUR

T1 - The Role of Interleukin-33 in Organ Fibrosis

AU - Di Carmine, Samuele

AU - Scott, Molly M.

AU - McLean, Mairi H.

AU - McSorley, Henry J.

N1 - Funding Information: Tenovus Ph.D. studentship to Molly M Scott. MRS/AZ PhD studentship to Samuele Di Carmine.

PY - 2022/9/26

Y1 - 2022/9/26

N2 - Interleukin-33 (IL-33) is highly expressed in the nucleus of cells present at barrier sites and signals via the suppression of tumorigenicity 2 receptor (ST2). IL-33 signalling via ST2 is essential for return to tissue homeostasis after acute inflammation, promoting fibrinogenesis and wound healing at injury sites. However, this wound-healing response becomes aberrant during chronic or sustained inflammation, leading to TGF-β release, excessive extracellular matrix (ECM) deposition, and fibrosis. This review addresses the role of the IL-33 pathway in fibrotic diseases of the lung, liver, gastrointestinal tract, skin, kidney and heart. In the lung and liver, IL-33 release leads to the activation of profibrotic TGF-β, and in these sites, IL-33 has clear pro-fibrotic roles. In the gastrointestinal tract, skin and kidney, the role of IL-33 is more complex, being both pro-fibrotic and tissue protective. Finally, in the heart, IL-33 serves cardioprotective functions by favouring tissue healing and preventing cardiomyocyte death. Altogether, this review indicates the presence of an unclear and delicate balance between resolving and pro-fibrotic capabilities of IL-33, which has a central role in the modulation of type 2 inflammation and fibrosis in response to tissue injury.

AB - Interleukin-33 (IL-33) is highly expressed in the nucleus of cells present at barrier sites and signals via the suppression of tumorigenicity 2 receptor (ST2). IL-33 signalling via ST2 is essential for return to tissue homeostasis after acute inflammation, promoting fibrinogenesis and wound healing at injury sites. However, this wound-healing response becomes aberrant during chronic or sustained inflammation, leading to TGF-β release, excessive extracellular matrix (ECM) deposition, and fibrosis. This review addresses the role of the IL-33 pathway in fibrotic diseases of the lung, liver, gastrointestinal tract, skin, kidney and heart. In the lung and liver, IL-33 release leads to the activation of profibrotic TGF-β, and in these sites, IL-33 has clear pro-fibrotic roles. In the gastrointestinal tract, skin and kidney, the role of IL-33 is more complex, being both pro-fibrotic and tissue protective. Finally, in the heart, IL-33 serves cardioprotective functions by favouring tissue healing and preventing cardiomyocyte death. Altogether, this review indicates the presence of an unclear and delicate balance between resolving and pro-fibrotic capabilities of IL-33, which has a central role in the modulation of type 2 inflammation and fibrosis in response to tissue injury.

KW - IL-33

KW - fibrosis

KW - acute injury

KW - chronic injury

KW - wound healing

U2 - 10.1093/discim/kyac006

DO - 10.1093/discim/kyac006

M3 - Review article

SN - 2754-2483

JO - Discovery Immunology

JF - Discovery Immunology

ER -