Anti-Inflammatory Mechanisms of Annexin Proteins in Immune Regulation

Annexin proteins, particularly Annexin A1, orchestrate the resolution of inflammation through coordinated actions on immune and vascular cells. By binding to phospholipid membranes in a calcium-dependent manner, these proteins limit neutrophil extravasation and promote timely apoptosis, thereby preventing excessive tissue damage. Annexins also enhance monocyte recruitment and drive differentiation towards pro-resolving macrophage phenotypes, facilitating the clearance of apoptotic cells via efferocytosis. Engagement of formyl peptide receptors triggers intracellular signalling that suppresses pro-inflammatory cytokine release and upholds anti-inflammatory mediator production, such as interleukin-10. Intracellular pools of annexin further influence gene expression programmes and cytoskeletal dynamics, reinforcing homeostasis. Together, these multifaceted mechanisms underpin the global significance of annexins as biomarkers and therapeutic candidates across cardiovascular, neurodegenerative and oncological settings.

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Anti-Inflammatory Mechanisms of Annexin Proteins in Immune Regulation publication trend

The graph below shows the total number of articles in anti-inflammatory mechanisms of annexin proteins in immune regulation across all publications each year (not limited to Nature Index journals).

Technical terms

Annexin A1: A calcium-dependent phospholipid-binding protein that mediates resolution of inflammation and regulates cell signalling.

Formyl Peptide Receptor 2 (FPR2): A G protein-coupled receptor that transduces the anti-inflammatory and pro-resolving signals of annexin peptides.

Mimetic peptide (Ac2-26): A synthetic fragment derived from the N-terminus of Annexin A1, retaining its immunoregulatory functions.

Macrophage polarization: The process by which macrophages adopt pro-inflammatory (M1) or anti-inflammatory (M2) functional states.

Efferocytosis: The clearance of apoptotic cells by phagocytes, a critical step in terminating inflammation.

References

1. Loss of Endothelial Annexin A1 Aggravates Inflammation‐Induched Vascular Aging. Advanced Science (2024).
2. The Annexin-A1 mimetic RTP-026 promotes acute cardioprotection through modulation of immune cell activation. Pharmacological Research (2023).
3. Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance. Journal of Immunology Research (2016).
4. Annexin A1: Uncovering the Many Talents of an Old Protein. International Journal of Molecular Sciences (2018).
5. Annexin A1 Interaction with the FPR2/ALX Receptor IDENTIFICATION OF DISTINCT DOMAINS AND DOWNSTREAM ASSOCIATED SIGNALING*. Journal of Biological Chemistry (2012).
6. Targeting of Annexin A1 in Tumor-associated Macrophages as a therapeutic strategy for hepatocellular carcinoma. Biochemical Pharmacology (2023).
7. Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment. Scientific Reports (2017).