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Annexin A1: potential for glucocorticoid sparing in RA

Nature Reviews Rheumatology volume 9, pages 595–603 (2013)Cite this article

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Abstract

Glucocorticoids have broad-ranging and powerful anti-inflammatory and immunomodulatory effects. Unsurprisingly, therefore, glucocorticoids are widely and persistently used to treat a large number of inflammatory diseases, including rheumatoid arthritis (RA), despite the well-described adverse effects of these drugs. Annexin A1 is a glucocorticoid-induced molecule that is known to replicate many of the described anti-inflammatory effects of glucocorticoids. In addition to the well-documented roles of this protein in neutrophil function, emerging evidence suggests that annexin A1 is involved in the modulation of T-cell function and the adaptive immune responses relevant to RA. Interest in annexin A1 was renewed after the delineation of the receptors for this protein. This breakthrough also led to advances in our understanding of anti-inflammatory annexin A1 mimetic peptides and agonistic compounds targeting these receptors, particularly those specific for the receptor N-formyl peptide receptor 2 (FPR2). Herein, we review the current knowledge of the biological activities of annexin A1 and their relevance to RA pathogenesis. We also discuss the potential of annexin A1 mimics and strategies aimed at potentiating annexin A1 signalling to become viable approaches to minimizing glucocorticoid use in RA and other inflammatory disorders.

Key Points

  • Glucocorticoids have powerful anti-inflammatory effects; the glucocortoid-induced protein annexin A1 mediates many of these

  • Annexin A1 has important and well-documented influences on inflammatory mechanisms involving the innate immune system, which are relevant to rheumatoid arthritis (RA) pathogenesis

  • Emerging data also support a role for annexin A1 in modulating the adaptive immune responses that are particularly relevant to the pathogenesis of RA

  • The cellular receptors for annexin A1, which include the N-formyl peptide receptor 2 (FPR2; also known as lipoxin A4 receptor or ALX), have now been delineated

  • Annexin A1, annexin A1 mimetic peptides and agonists of the N-formyl peptide receptors have the potential to reproduce the therapeutic anti-inflammatory effects of glucocorticoids without their adverse effects on other biological systems

  • Therapies directly targeting the annexin A1 signalling pathway could enable a novel glucocorticoid-sparing approach to the treatment of RA

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Figure 1: Pathway of glucocorticoid-induced annexin A1 expression.
Figure 2: The FPR2-mediated anti-inflammatory and immune modulatory effects of annexin A1.
Figure 3: Receptor–ligand complexity of annexin A1 and its mimetics.

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  1. Department of Medicine, Centre for Inflammatory Diseases, Southern Clinical School, Monash University Faculty of Medicine, Nursing and Health Sciences, Monash Medical Centre, Clayton, 3168, VIC, Australia

    Yuan H. Yang, Eric Morand & Michelle Leech

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Y. H. Yang researched the data for the article. All authors provided substantial contribution to discussions of content, contributed equally to writing the article and to review and/or editing of the manuscript before submission.

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Yang, Y., Morand, E. & Leech, M. Annexin A1: potential for glucocorticoid sparing in RA. Nat Rev Rheumatol 9, 595–603 (2013). https://doi.org/10.1038/nrrheum.2013.126

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