In normal individuals (i.e., with transmigration-competent neutrophils), recruited neutrophils regulate IL-23 production by tissue phagocytes (“PHAG”; e.g., macrophages) and hence the expression of IL-17 by adaptive and innate immune cells (e.g., Th17, γδ T cells, and innate lymphoid cells [ILC]) [11]. In contrast, LAD-I, which impairs neutrophil transmigration (1) leads to dysregulation of IL-23 (2) and hence overproduction of the inflammatory and bone-resorptive cytokine IL-17 (3). Inflammatory tissue breakdown products serve as nutrients for the local microbiome, thereby contributing to its overgrowth (4). Microbial products translocated into the lesions (for instance, LPS [44]) persistently stimulate the disinhibited IL-23–IL-17 axis (5) amplifying the destructive response. From ref. [18]. Used by permission.