Innate immune cross-talk: The central role of neutrophils and macrophages in ANCA-associated vasculitis | CU Experts

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare but severe autoimmune diseases characterized by necrotizing inflammation of small blood vessels, leading to organ damage, particularly in the kidneys and respiratory tract. The current understanding of AAV pathogenesis has moved beyond a simple model of autoantibody-mediated damage to recognize a complex, self-sustaining inflammatory circuit. Central to this circuit is a dysregulated triad between neutrophils, macrophages, and the vascular endothelium. This review synthesizes our current understanding of this innate immune axis, detailing the pathogenic sequence from the initial loss of tolerance to the subsequent inflammatory priming event that triggers the pathogenic activation of neutrophils. The chronicity of AAV arises from powerful feed-forward amplification loops that sustain inflammation, which are cemented by the active suppression of the body's intrinsic resolution pathways. Finally, we discuss how advanced bioengineered platforms, such as vasculitis-on-a-chip models, are essential for deconstructing this complex pathology and are poised to accelerate the development of a new generation of targeted, pro-resolution therapies. This review provides a comprehensive framework for understanding the central role of neutrophil–macrophage cross-talk in the perpetuation of AAV.

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