TY - JOUR
T1 - Monocytes and macrophages in ANCA-associated vasculitis
AU - Vegting, Yosta
AU - Vogt, Liffert
AU - Anders, Hans-Joachim
AU - de Winther, Menno P. J.
AU - Bemelman, Frederike J.
AU - Hilhorst, Marc L.
N1 - Funding Information: This work was supported by the Dutch Kidney Foundation [grant number 19OK007 ]. Publisher Copyright: © 2021 The Author(s)
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are characterized by inflammation of small-to-medium-sized blood vessels and the presence of autoantibodies against cytoplasmic proteases sited in neutrophils and monocytes. Increasing evidence indicates a substantial role of monocytes and macrophages in the pathogenesis of AAV. Activated monocytes and macrophages contribute to necroinflammation in peripheral vasculitic lesions as well as to central and peripheral mechanisms of autoimmunity. The intermediate monocyte subset (CD14++CD16+) is increased and monocytes show elevated expression of CD14, Toll-like receptor 2/4, MHCII and integrins, likely reflecting activation and increased monocyte extravasation. Monocytes differentiate locally predominantly into alternatively activated (M2) macrophages, which are known for cell-clearance and phagocytosis, but may ultimately lead to fibrosis. Phagocytotic function of macrophages can be impaired by surface expression of cytoplasmic proteases on apoptotic neutrophils and causes release of inflammatory cytokines and immunogenic contents, presumably resulting in a vicious circle of increased neutrophil, T and B cell activation and consequent ANCA production. Considering their crucial role in initiating necroinflammation as well as fibrogenesis, monocytes and macrophages may represent a logic first-line target for new treatment options in AAV.
AB - Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are characterized by inflammation of small-to-medium-sized blood vessels and the presence of autoantibodies against cytoplasmic proteases sited in neutrophils and monocytes. Increasing evidence indicates a substantial role of monocytes and macrophages in the pathogenesis of AAV. Activated monocytes and macrophages contribute to necroinflammation in peripheral vasculitic lesions as well as to central and peripheral mechanisms of autoimmunity. The intermediate monocyte subset (CD14++CD16+) is increased and monocytes show elevated expression of CD14, Toll-like receptor 2/4, MHCII and integrins, likely reflecting activation and increased monocyte extravasation. Monocytes differentiate locally predominantly into alternatively activated (M2) macrophages, which are known for cell-clearance and phagocytosis, but may ultimately lead to fibrosis. Phagocytotic function of macrophages can be impaired by surface expression of cytoplasmic proteases on apoptotic neutrophils and causes release of inflammatory cytokines and immunogenic contents, presumably resulting in a vicious circle of increased neutrophil, T and B cell activation and consequent ANCA production. Considering their crucial role in initiating necroinflammation as well as fibrogenesis, monocytes and macrophages may represent a logic first-line target for new treatment options in AAV.
KW - ANCA-associated vasculitis
KW - Macrophage
KW - Monocyte
KW - Polarization
UR - http://www.scopus.com/inward/record.url?scp=85111506162&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.autrev.2021.102911
DO - https://doi.org/10.1016/j.autrev.2021.102911
M3 - Review article
C2 - 34298153
SN - 1568-9972
VL - 20
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
IS - 10
M1 - 102911
ER -