Bio

Academic Appointments


  • Visiting Assistant Professor, Medicine - Immunology & Rheumatology

Publications

All Publications


  • Neutrophil Extracellular Traps Induce Tissue-Invasive Macrophages in Granulomatosis with Polyangiitis Dominated by Ear, Nose and Throat Manifestations Akiyama, M., Ibrahim, N., Zeisbrich, M., Hwang, P., Goronzy, J., Weyand, C. WILEY. 2019
  • Metabolic Signatures of Pathogenic T Cells in Medium and Large Vessel Vasculitis Akiyama, M., Zhang, H., Watanabe, R., Maeda, T., Berry, G., Goronzy, J., Weyand, C. WILEY. 2019
  • GM-CSF Is a Pro-Inflammatory Cytokine in Experimental Vasculitis of Medium and Large Arteries Watanabe, R., Zhang, H., Maeda, T., Akiyama, M., Gandhi, R., Paolini, J., Berry, G., Weyand, C. WILEY. 2019
  • Cytokines, growth factors and proteases in medium and large vessel vasculitis CLINICAL IMMUNOLOGY Weyand, C. M., Watanabe, R., Zhang, H., Akiyama, M., Berry, G. J., Goronzy, J. J. 2019; 206: 33–41
  • Cytokines, growth factors and proteases in medium and large vessel vasculitis. Clinical immunology (Orlando, Fla.) Weyand, C. M., Watanabe, R., Zhang, H., Akiyama, M., Berry, G. J., Goronzy, J. J. 2019

    Abstract

    Giant cell arteritis and Takayasu arteritis are autoimmune vasculitides that cause aneurysm formation and tissue infarction. Extravascular inflammation consists of an intense acute phase response. Deeper understanding of pathogenic events in the vessel wall has highlighted the loss of tissue protective mechanisms, the intrusion of immune cells into "forbidden territory", and the autonomy of self-renewing vasculitic infiltrates. Adventitial vasa vasora critically control vessel wall access and drive differentiation of tissue-invasive T cells. Selected T cells establish tissue residency and build autonomous, self-sufficient inflammatory lesions. Pathogenic effector T cells intrude and survive due to failed immune checkpoint inhibition. Vasculitis-sustaining T cells and macrophages provide a broad portfolio of effector functions, involving heterogeneous populations of pro-inflammatory T cells and diverse macrophage subsets that ultimately induce wall capillarization and intimal hyperplasia. Redirecting diagnostic and therapeutic strategies from control of extravascular inflammatory markers to suppression of vascular inflammation will improve disease management.

    View details for PubMedID 30772599

  • Neutrophil Extracellular Traps Induce Tissue-Invasive Monocytes in Granulomatosis With Polyangiitis. Frontiers in immunology Akiyama, M., Zeisbrich, M., Ibrahim, N., Ohtsuki, S., Berry, G. J., Hwang, P. H., Goronzy, J. J., Weyand, C. M. 2019; 10: 2617

    Abstract

    Objective: Granulomatosis with polyangiitis (GPA) is a multi-organ vasculitic syndrome typically associated with neutrophil extracellular trap (NET) formation and aggressive tissue inflammation. Manifestations in head and neck (H&N) GPA include septal perforations, saddle-nose deformities, bony erosions of the orbital and sinus walls, middle ear damage and epiglottitis, indicative of bone, cartilage, and connective tissue destruction. Whether H&N-centric lesions engage disease pathways distinctive from the ischemic tissue damage in the lungs, kidneys, skin, and peripheral nerves is unknown. We have compared inflammatory responses triggered by neutrophilic NETs in patients with H&N GPA and systemic GPA (sGPA). Methods: Neutrophils and monocytes were isolated from the peripheral blood of patients with H&N GPA, sGPA, and age/gender matched healthy individuals. Neutrophil NETosis was induced. NETs were isolated and cocultured with monocytes. Gene induction was quantified by RT-PCR, protein upregulation by flow cytometry. Tissue invasiveness of monocytes was measured in a 3D collagen matrix system. Expression of MMP-9 in tissue-residing macrophages was assessed by immunohistochemistry in tissue biopsies. Results: Neutrophils from H&N GPA patients showed more intense NETosis with higher frequencies of netting neutrophils (P < 0.001) and release of higher amounts of NETs (P < 0.001). Isolated NETs from H&N GPA functioned as an inducer of danger-associated molecular patterns in monocytes; specifically, alarmin S100A9. NET-induced upregulation of monocyte S100A9 required recognition of DNA. S100A9 release resulted in the induction of metalloproteinases, including MMP-9, and enabled monocytes to invade into extracellular matrix. Anti-MMP-9 treatment attenuated the tissue invasiveness of monocytes primed with NETs from H&N GPA patients. MMP-9-producing macrophages dominated the tissue infiltrates in naso-sinal biopsies from H&N GPA patients. Conclusion: Distinct disease patterns in GPA are associated with differences in NET formation and NET content. H&N GPA patients with midline cartilaginous and bony lesions are highly efficient in generating NETs. H&N GPA neutrophils trigger the induction of the alarmin S100A9, followed by production of MMP-9, endowing monocytes with tissue-invasive capabilities.

    View details for DOI 10.3389/fimmu.2019.02617

    View details for PubMedID 31798577

    View details for PubMedCentralID PMC6874157

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