The neutrophil: A key resourceful agent in immune‐mediated vasculitis

Summary The term “vasculitis” refers to a group of rare immune‐mediated diseases characterized by the dysregulated immune system attacking blood vessels located in any organ of the body, including the skin, lungs, and kidneys. Vasculitides are classified according to the size of the vessel that is affected. Although this observation is not specific to small‐, medium‐, or large‐vessel vasculitides, patients show a high circulating neutrophil‐to‐lymphocyte ratio, suggesting the direct or indirect involvement of neutrophils in these diseases. As first responders to infection or inflammation, neutrophils release cytotoxic mediators, including reactive oxygen species, proteases, and neutrophil extracellular traps. If not controlled, this dangerous arsenal can injure the vascular system, which acts as the main transport route for neutrophils, thereby amplifying the initial inflammatory stimulus and the recruitment of immune cells. This review highlights the ability of neutrophils to “set the tone” for immune cells and other cells in the vessel wall. Considering both their long‐established and newly described roles, we extend their functions far beyond their direct host‐damaging potential. We also review the roles of neutrophils in various types of primary vasculitis, including immune complex vasculitis, anti‐neutrophil cytoplasmic antibody‐associated vasculitis, polyarteritis nodosa, Kawasaki disease, giant cell arteritis, Takayasu arteritis, and Behçet's disease.