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ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity

Author

Listed:
  • Matteo Massara

    (Humanitas Clinical and Research Center
    Università degli Studi di Milano)

  • Ornella Bonavita

    (Humanitas Clinical and Research Center
    Università degli Studi di Milano)

  • Benedetta Savino

    (Humanitas Clinical and Research Center
    Università degli Studi di Milano)

  • Nicoletta Caronni

    (Humanitas Clinical and Research Center
    Università degli Studi di Milano)

  • Valeria Mollica Poeta

    (Humanitas Clinical and Research Center
    Humanitas University)

  • Marina Sironi

    (Humanitas Clinical and Research Center)

  • Elisa Setten

    (Humanitas Clinical and Research Center
    Università degli Studi di Milano)

  • Camilla Recordati

    (Fondazione Filarete)

  • Laura Crisafulli

    (Humanitas Clinical and Research Center
    CNR)

  • Francesca Ficara

    (Humanitas Clinical and Research Center
    CNR)

  • Alberto Mantovani

    (Humanitas Clinical and Research Center
    Humanitas University
    Queen Mary University of London)

  • Massimo Locati

    (Humanitas Clinical and Research Center
    Università degli Studi di Milano)

  • Raffaella Bonecchi

    (Humanitas Clinical and Research Center
    Humanitas University)

Abstract

Atypical chemokine receptors (ACKRs) are regulators of leukocyte traffic, inflammation, and immunity. ACKR2 is a scavenger for most inflammatory CC chemokines and is a negative regulator of inflammation. Here we report that ACKR2 is expressed in hematopoietic precursors and downregulated during myeloid differentiation. Genetic inactivation of ACKR2 results in increased levels of inflammatory chemokine receptors and release from the bone marrow of neutrophils with increased anti-metastatic activity. In a model of NeuT-driven primary mammary carcinogenesis ACKR2 deficiency is associated with increased primary tumor growth and protection against metastasis. ACKR2 deficiency results in neutrophil-mediated protection against metastasis in mice orthotopically transplanted with 4T1 mammary carcinoma and intravenously injected with B16F10 melanoma cell lines. Thus, ACKR2 is a key regulator (checkpoint) of mouse myeloid differentiation and function and its targeting unleashes the anti-metastatic activity of neutrophils in mice.

Suggested Citation

  • Matteo Massara & Ornella Bonavita & Benedetta Savino & Nicoletta Caronni & Valeria Mollica Poeta & Marina Sironi & Elisa Setten & Camilla Recordati & Laura Crisafulli & Francesca Ficara & Alberto Mant, 2018. "ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03080-8
    DOI: 10.1038/s41467-018-03080-8
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