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The role of platelets in immune-mediated inflammatory diseases

Nature Reviews Immunology volume 23, pages 495–510 (2023)Cite this article

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An Author Correction to this article was published on 21 March 2023

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Abstract

Immune-mediated inflammatory diseases (IMIDs) are characterized by excessive and uncontrolled inflammation and thrombosis, both of which are responsible for organ damage, morbidity and death. Platelets have long been known for their role in primary haemostasis, but they are now also considered to be components of the immune system and to have a central role in the pathogenesis of IMIDs. In patients with IMIDs, platelets are activated by disease-specific factors, and their activation often reflects disease activity. Here we summarize the evidence showing that activated platelets have an active role in the pathogenesis and the progression of IMIDs. Activated platelets produce soluble factors and directly interact with immune cells, thereby promoting an inflammatory phenotype. Furthermore, platelets participate in tissue injury and promote abnormal tissue healing, leading to fibrosis. Targeting platelet activation and targeting the interaction of platelets with the immune system are novel and promising therapeutic strategies in IMIDs.

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Fig. 1: Effects of platelet activation.
Fig. 2: Activated platelets interact with and activate innate and adaptive immune cells.
Fig. 3: Role of the P-selectin–PSGL1 axis in immune-mediated inflammatory disease.
Fig. 4: Potential therapeutic strategies to target platelets in immune-mediated inflammatory disease.

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Acknowledgements

M.S. is supported by academic sources including the Société Française de Rhumatologie, the Institut pour la Santé et la Recherche Médicale and the Bettencourt-Schueller Fondation. E.B. is recipient of an award from the Fonds de Recherche en Santé du Québec. P.B. is supported by the Fondation pour la Recherche Médicale, Société Française de Rhumatologie, Foundation for Research in Rheumatology (FOREUM) and Fondation Arthritis.

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Authors and Affiliations

  1. Service de Rhumatologie, Centre de référence des maladies auto-immunes systémiques rares RESO, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Marc Scherlinger

  2. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Marc Scherlinger & George C. Tsokos

  3. Laboratoire d’ImmunoRhumatologie Moléculaire UMR_S 1109, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France

    Marc Scherlinger

  4. Service de Rhumatologie, Centre de référence des maladies auto-immunes systémiques rares RESO, Hôpital Pellegrin, Centre Hospitalier Universitaire, Bordeaux, France

    Christophe Richez

  5. CNRS-UMR 5164, ImmunoConcept, Université de Bordeaux, Bordeaux, France

    Christophe Richez & Patrick Blanco

  6. Centre de Recherche du Centre Hospitalier Universitaire de Québec–Université Laval, Quebec City, Quebec, Canada

    Eric Boilard

  7. Centre de Recherche ARThrite, Université Laval, Quebec City, Quebec, Canada

    Eric Boilard

  8. Laboratoire d’Immunologie et Immunogénétique, FHU ACRONIM, Hôpital Pellegrin, Centre Hospitalier Universitaire, Bordeaux, France

    Patrick Blanco

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Contributions

M.S. wrote the first draft and conceptualized the figures. E.B., G.C.T., C.R. and P.B. edited the manuscript and suggested additions. All authors approved the final version of the manuscript.

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Correspondence to Marc Scherlinger or Patrick Blanco.

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Competing interests

C.R. has received consulting or speaker fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Biogen, Eli Lilly, GlaxoSmithKline, Janssen Novartis and Pfizer and grants from Biogen, Eli Lilly and Nordic Pharma, all unrelated to this work. M.S. has received consulting fees from Sandoz, Amgen and Nordic Pharma, all unrelated to this work. The other authors report no competing interests.

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Glossary

Antineutrophil cytoplasmic antibody

A type of autoantibody that targets neutrophil components and is characteristic of antineutrophil cytoplasmic antibody-associated vasculitis.

Antiphospholipid syndrome

(APS). An autoimmune disorder characterized by antiphospholipid antibodies responsible for arterial and venous thrombosis and obstetric issues.

Clopidogrel

An anti-aggregation therapy that targets the platelet purine receptor P2Y12, which is widely prescribed for the prevention of cardiovascular disease in patients at high risk (such as patients with a history of myocardial infarction).

Disseminated intravascular coagulation

A critical medical condition characterized by widespread and dysregulated clotting throughout the blood vessels.

Extracellular vesicles

Small (10–1,000 nm) vesicles surrounded by a lipid bilayer that are released from a cell (often after activation) and that contain soluble factors and surface molecules from that cell.

Ferroptosis

A form of programmed cell death that is dependent on intracellular iron, characterized by the intracellular accumulation of lipid peroxides.

Immune thrombocytopenia

(ITP). An autoimmune disorder characterized by severe thrombocytopenia secondary to immune destruction of platelets that is responsible for increased bleeding risk.

Inflammatory bowel disease

(IBD). A group of immune-mediated inflammatory diseases such as Crohn’s disease or ulcerative colitis characterized by inflammation of the bowel wall.

Ischaemia–reperfusion injury

A condition in which tissue damage occurs after blood flow is restored to an ischaemic tissue owing to the local release of toxic factors after reperfusion.

Mesangial cells

Mesenchymal cells of the kidney that are responsible for the architecture of the glomeruli.

NETosis

A form of programmed cell death by which neutrophils release the contents of their cytoplasm and nucleus (including DNA and histones) into the extracellular milieu, often in the context of infection or autoimmunity.

Primary haemostasis

The primary response to ensure blood vessel integrity upon injury, which involves platelets, subendothelial matrix tissue factor and circulating fibrinogen.

Podocytes

Specialized epithelial cells that form the finely fenestrated lining of the kidney glomeruli and are responsible for blood filtration with minimal loss of protein in the urine.

Psoriasis

A frequent skin inflammatory disease characterized by widespread scaly and itchy patches, which can be associated with inflammatory arthritis (psoriatic arthritis).

Raynaud phenomenon

A condition in which the blood vessels in the extremities constrict upon exposure to cold, resulting in skin colour changes (typically white, blue then red) and pain. The condition may be benign (Raynaud disease) or associated with an autoimmune disease (secondary Raynaud phenomenon).

Rheumatoid arthritis

A non-rare (prevalence of 0.5% in high-income countries) autoimmune disease characterized by widespread inflammation and destruction of joints, as well as involvement of other organs (lungs and eyes).

Sjögren syndrome

A connective tissue disorder characterized by the involvement of exocrine glands, causing dry eyes and/or mouth, as well as systemic symptoms.

Systemic lupus erythematosus

(SLE). A prototypical systemic autoimmune disease characterized by the production of antibodies to DNA and the involvement of a wide range of organs.

Systemic sclerosis

A connective tissue disorder characterized by vasculopathy, autoimmunity and excessive fibrosis.

von Willebrand factor

A multimeric blood glycoprotein involved in platelet adhesion to a wound and which is necessary for the initial steps of blood clotting.

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Scherlinger, M., Richez, C., Tsokos, G.C. et al. The role of platelets in immune-mediated inflammatory diseases. Nat Rev Immunol 23, 495–510 (2023). https://doi.org/10.1038/s41577-023-00834-4

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