Amphiregulin in cellular physiology, health, and disease: Potential use as a biomarker and therapeutic target

Abstract

Amphiregulin (AREG), which acts as one of the ligands for epidermal receptor growth factor receptor (EGFR), plays a crucial role in tissue repair, inflammation, and immunity. AREG is synthesized as membrane‐anchored pre‐protein, and is excreted after proteolytic cleavage, and serves as an autocrine or paracrine factor. After engagement with the EGFR, AREG triggers a cascade of signaling events required for many cellular physiological processes including metabolism, cell cycle, and proliferation. Under different inflammatory and pathogenic conditions, AREG is expressed by various activated immune cells that orchestrate both tolerance and host resistance mechanisms. Several factors including xenobiotics, cytokines, and inflammatory lipids have been shown to trigger AREG gene expression and release. In this review, we discuss the structure, function, and regulation of AREG, its role in tissue repair, inflammation, and homeostasis as well as the potential of AREG as a biomarker and therapeutic target.

Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes

“…15a, b ). These findings indicate that our iLD-IL-2 dosing regimen induces a shared Day 55 gene expression signature in different cell types, which featured most prominently the upregulation of Cytokine Inducible SH2 Containing Protein ( CISH ), a gene encoding a well-characterised negative regulator of cytokine signalling, and the downregulation of Amphiregulin ( AREG ), a secreted TNF-inducible protein with pleiotropic roles in inflammation 36 . We also noted an enrichment of genes associated with cytokine signalling, most notably in the tumour necrosis factor (TNF) signalling pathway, which in addition to CISH and AREG , also included TNFSF14 , TNFSF10 , STAT1 , SGK1 , NFKBIZ , NFKBIA , DUSP2 , DUSP4 , DUSP5 , RGS1 and TNFAIP3 (Fig.…”

Low-dose IL-2 reduces IL-21+T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients

“…14a,b ). These findings indicate that our iLD-IL-2 dosing regimen induces a shared Day 55 gene expression signature in different cell types, which featured most prominently the upregulation of Cytokine Inducible SH2 Containing Protein ( CISH ), a gene encoding a well-characterised negative regulator of cytokine signalling, and the downregulation of Amphiregulin ( AREG ), a secreted TNF-inducible protein with pleiotropic roles in inflammation 38 . We also noted an enrichment of genes associated with cytokine signalling, most notably in the tumour necrosis factor (TNF) signalling pathway, which in addition to CISH and AREG , also included TNFSF14 , TNFSF10 , STAT1 , SGK1 , NFKBIZ , NFKBIA , DUSP2 , DUSP4 , DUSP5 , RGS1 and TNFAIP3 ( Fig.…”

Understanding COVID-19 in children: immune determinants and post-infection conditions

“…A particular type of lymphocyte, the innate lymphoid cells (ILCs), may contribute to host resistance toward SARS-CoV-2 infection and promote restoration of tissue damage by producing amphiregulin, a type-II cytokine. 64 These cells are known in animal models to ensure tissue integrity and regulate the innate and adaptive immune response with the effect of decreasing disease severity. 65 In a recent study, Silverstein et al showed that the number of ILCs in the blood of patients with SARS-CoV-2 infection was inversely correlated with age and was lower in men, reflecting a higher risk associated with male sex and older age.…”