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Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment

Author

Listed:
  • Gurpanna Saggu

    (Brigham and Women’s Hospital & Harvard Medical School)

  • Koshu Okubo

    (Brigham and Women’s Hospital & Harvard Medical School)

  • Yunfeng Chen

    (Georgia Institute of Technology)

  • Ravi Vattepu

    (Massachusetts General Hospital & Harvard Medical School)

  • Naotake Tsuboi

    (Brigham and Women’s Hospital & Harvard Medical School
    Fujita Health University School of Medicine)

  • Florencia Rosetti

    (Brigham and Women’s Hospital & Harvard Medical School
    Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán)

  • Xavier Cullere

    (Brigham and Women’s Hospital & Harvard Medical School)

  • Nathaniel Washburn

    (Momenta Pharmaceuticals)

  • Suhail Tahir

    (Brigham and Women’s Hospital & Harvard Medical School)

  • Aaron M. Rosado

    (Georgia Institute of Technology)

  • Steven M. Holland

    (National Institutes of Health)

  • Robert M. Anthony

    (Massachusetts General Hospital & Harvard Medical School)

  • Mehmet Sen

    (University of Houston)

  • Cheng Zhu

    (Georgia Institute of Technology)

  • Tanya N. Mayadas

    (Brigham and Women’s Hospital & Harvard Medical School)

Abstract

Vascular-deposited IgG immune complexes promote neutrophil recruitment, but how this process is regulated is still unclear. Here we show that the CD18 integrin Mac-1, in its bent state, interacts with the IgG receptor FcγRIIA in cis to reduce the affinity of FcγRIIA for IgG and inhibit FcγRIIA-mediated neutrophil recruitment under flow. The Mac-1 rs1143679 lupus-risk variant reverses Mac-1 inhibition of FcγRIIA, as does a Mac-1 ligand and a mutation in Mac-1’s ligand binding αI-domain. Sialylated complex glycans on FcγRIIA interact with the αI-domain via divalent cations, and this interaction is required for FcγRIIA inhibition by Mac-1. Human neutrophils deficient in CD18 integrins exhibit augmented FcγRIIA-dependent recruitment to IgG-coated endothelium. In mice, CD18 integrins on neutrophils dampen IgG-mediated neutrophil accumulation in the kidney. In summary, cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 alters the threshold for IgG-mediated neutrophil recruitment. A disruption of this interaction may increase neutrophil influx in autoimmune diseases.

Suggested Citation

  • Gurpanna Saggu & Koshu Okubo & Yunfeng Chen & Ravi Vattepu & Naotake Tsuboi & Florencia Rosetti & Xavier Cullere & Nathaniel Washburn & Suhail Tahir & Aaron M. Rosado & Steven M. Holland & Robert M. A, 2018. "Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07506-1
    DOI: 10.1038/s41467-018-07506-1
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