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The role of neutrophils in rheumatic disease-associated vascular inflammation

Nature Reviews Rheumatology volume 18, pages 158–170 (2022)Cite this article

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Abstract

Vascular pathologies underpin and intertwine autoimmune rheumatic diseases and cardiovascular conditions, and atherosclerosis is increasingly recognized as the leading cause of morbidity in conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Neutrophils, important cells in the innate immune system, exert their functional effects in tissues via a variety of mechanisms, including the generation of neutrophil extracellular traps and the production of reactive oxygen species. Neutrophils have been implicated in the pathogenesis of several rheumatic diseases, and can also intimately interact with the vascular system, either through modulating endothelial barriers at the blood–vessel interface, or through associations with platelets. Emerging data suggest that neutrophils also have an important role maintaining homeostasis in individual organs and can protect the vascular system. Furthermore, studies using high-dimensional omics technologies have advanced our understanding of neutrophil diversity, and immature neutrophils are receiving new attention in rheumatic diseases including SLE and systemic vasculitis. Developments in genomic, imaging and organoid technologies are beginning to enable more in-depth investigations into the pathophysiology of vascular inflammation in rheumatic diseases, making now a good time to re-examine the full scope of roles of neutrophils in these processes.

Key points

  • Neutrophils are heterogeneous and have diversified phenotypes and functions, such as reactive oxygen species-producing immature neutrophils and neutrophil extracellular trap-producing mature neutrophils.

  • Neutrophils participate in the progression of disease from onset to chronic inflammation affecting multiple organs and tissues in rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and vasculitis.

  • Vascular inflammation in rheumatic diseases is associated with cardiovascular complications, such as atherosclerosis, which are a leading cause of morbidity and mortality.

  • Neutrophils, both mature and immature, have an essential role in initial endothelial activation and dysfunction associated with vascular inflammation and atherosclerosis.

  • Immune complexes in rheumatic diseases with well-defined autoantibodies excessively activate neutrophils to induce endothelial damage.

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Fig. 1: Proposed model of neutrophil-mediated vascular inflammation.

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  1. Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK

    Lihui Wang & Irina A. Udalova

  2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK

    Raashid Luqmani

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L.W. researched data for this article. R.L. and I.A.U. provided substantial contributions to discussions of content. L.W. and I.A.U. wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Wang, L., Luqmani, R. & Udalova, I.A. The role of neutrophils in rheumatic disease-associated vascular inflammation. Nat Rev Rheumatol 18, 158–170 (2022). https://doi.org/10.1038/s41584-021-00738-4

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