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Review
. 2022 May;166(1):2-16.
doi: 10.1111/imm.13455. Epub 2022 Mar 1.

Annexin-A1: The culprit or the solution?

Lauren Kelly  1 , Sarah McGrath  1 , Lewis Rodgers  1 , Kathryn McCall  1 , Aysin Tulunay Virlan  1 , Fiona Dempsey  2 , Scott Crichton  2 , Carl S Goodyear  1
Affiliations
Review

Annexin-A1: The culprit or the solution?

Lauren Kelly et al. Immunology. 2022 May.

Abstract

Annexin-A1 has a well-defined anti-inflammatory role in the innate immune system, but its function in adaptive immunity remains controversial. This glucocorticoid-induced protein has been implicated in a range of inflammatory conditions and cancers, as well as being found to be overexpressed on the T cells of patients with autoimmune disease. Moreover, the formyl peptide family of receptors, through which annexin-A1 primarily signals, has also been implicated in these diseases. In contrast, treatment with recombinant annexin-A1 peptides resulted in suppression of inflammatory processes in murine models of inflammation. This review will focus on what is currently known about annexin-A1 in health and disease and discuss the potential of this protein as a biomarker and therapeutic target.

Keywords: Annexin-A1; biomarker; cancer; cell signalling inflammation; formyl peptide receptors; immune response.

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Conflict of interest statement

Dr Fiona Dempsey and Scott Crichton are employed by the biopharmaceutical company Medannex, which is working to develop therapeutic antibodies targeting annexin‐A1.

Figures

FIGURE 1
FIGURE 1
Annexin‐A1 alone and in the presence of calcium. Ribbon diagrams showing full‐length annexin‐A1 (ANXA1) without calcium binding (left, protein database code 1HM6) and with calcium binding (right, protein database code 1MCX). The N terminus is highlighted in red and calcium ions are in grey. The image shows a conformational change in the ANXA1 protein upon calcium binding (B), exposing the N terminus for subsequent binding to membrane phospholipids to facilitate its functions. The images were taken from the protein database using the iCn3D [ software and edited using Biorender.com
FIGURE 2
FIGURE 2
Actions of FPR2 are cell type dependent. Internalization and binding of glucocorticoids (GCs) to their receptor triggers the production of ANXA1. ANXA1 is externalized where it can bind to FPR2 on the cell surface initiating functions such as apoptosis and inhibition of migration in neutrophils and enhanced recruitment and efferocytosis in monocytes. Image created with Biorender.com
FIGURE 3
FIGURE 3
ANXA1 structure. ANXA1 is composed of four repeating C terminal motifs and an N terminal domain consisting of the Ac2‐26 peptide. Both full‐length ANXA1 and Ac2‐26 have been shown to interreact with the FPRs. The sequence of Ac‐26 is shown, along with its acetyl group N terminus constructed for stability and delay of protein degradation. Image adapted from Gavins et al [ and created using Biorender.com
FIGURE 4
FIGURE 4
ANXA1 Triggers MAP kinase signalling. ANXA1 binding to FPR2 on the plasma membrane can trigger signalling of MAP kinases. This has different outcomes depending on the cell type affected, including monocyte differentiation, neutrophil apoptosis and T‐cell proliferation. Adapted from D’Acquisto et al [ Image created with Biorender.com
See this image and copyright information in PMC

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