2. Academic Validation
  3. Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education

Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education

  • J Exp Med. 2021 Jul 5;218(7):e20201353. doi: 10.1084/jem.20201353.
Jan Rossaint 1,  Katharina Thomas 1,  Sina Mersmann 1,  Jennifer Skupski 1,  Andreas Margraf 1,  Tobias Tekath 2,  Charlotte C Jouvene 3,  Jesmond Dalli 3,  Andres Hidalgo 4,  Sven G Meuth 5,  Oliver Soehnlein 6 7 8,  Alexander Zarbock 1
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
  • 2 Institute of Medical Informatics, University of Münster, Münster, Germany.
  • 3 William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • 4 Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
  • 5 Clinic of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
  • 6 Institute for Experimental Pathology, Center for Molecular Biology of Inflammation, University of Münster, Münster, Germany.
  • 7 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • 8 Institute for Cardiovascular Prevention, Ludwig-Maximillians-Universität München, Munich, Germany.
PMID: 34014253 DOI: 10.1084/jem.20201353
Abstract

Beyond hemostasis, platelets actively participate in immune cell recruitment and host defense, yet their potential in the resolution of inflammatory processes remains unknown. Here, we demonstrate that platelets are recruited into the lung together with neutrophils during the onset of inflammation and alongside regulatory T (T reg) cells during the resolution phase. This partnering dichotomy is regulated by differential adhesion molecule expression during resolution. Mechanistically, intravascular platelets form aggregates with T reg cells, a prerequisite for their recruitment into the lung. This interaction relies on platelet activation by sCD40L and platelet P-selectin binding to PSGL-1 on T reg cells. Physical platelet-T reg cell interactions are necessary to modulate the transcriptome and instruct T reg cells to release the anti-inflammatory mediators IL-10 and TGFβ. Notably, the presence of platelet-T reg cell aggregates in the lung was also required for macrophage transcriptional reprogramming, polarization toward an anti-inflammatory phenotype, and effective resolution of pulmonary inflammation. Thus, platelets partner with successive immune cell subsets to orchestrate both the initiation and resolution of inflammation.

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