Loss of monocyte-derived myeloid cells resident to the human endolymphatic sac in Meniere’s disease

Myeloid cells expressing ionized calcium-binding adapter molecule 1 (Iba1+) broadly populate the inner ear, where they likely perform key tissue homeostatic functions including the phagocytosis of cellular debris and apoptotic bodies, modulation of inflammatory responses, neuroprotection, tissue repair, and potentially synaptic remodeling. Although the endolymphatic sac (ES)—a non-sensory epithelial appendage—is considered a key site for immune surveillance and homeostasis in the inner ear, the presence and function of resident Iba1⁺ myeloid cells in the human ES remain unexplored. This gap is particularly significant given that unexplained degeneration of the ES has been implicated in the pathogenesis of Meniere’s disease (MD), a chronic and progressive inner ear disorder. Here, we leveraged immunohistochemical analysis of Iba1, the microglial marker TMEM119, the lymphatic endothelial marker LYVE1, and the pro-inflammatory cytokine interleukin-1β (IL-1β) in tissue sections and whole-mount preparations of postmortem human ES specimens from MD patients and healthy controls, as well as in adult murine (C57BL6/J6) ES to demonstrate that (i) ES-associated myeloid cells densely populate both murine and human ES and are predominantly Iba1⁺/TMEM119⁻, consistent with a peripheral, bone marrow-derived monocyte lineage; (ii) the ES epithelium robustly expresses the paracrine signaling protein IL-1β, which may act as a direct or indirect chemoattractant for circulating monocytes; (iii) a dense network of dural lymphatic vessels converges on the ES, potentially facilitating recruitment of circulating monocytes; and (iv) degenerated ES tissues from MD patients exhibit a significant reduction in Iba1⁺ myeloid cells. Collectively, these data support a model in which resident, peripherally derived Iba1⁺/TMEM119⁻ myeloid cells are attracted by the healthy ES epithelium through IL-1β‐mediated recruitment and local lymphatic trafficking, possibly to execute tissue homeostatic and immune surveillance functions. Although the temporal sequence of ES degeneration and myeloid cell loss remains to be elucidated, our results suggest immune dysregulation as a potential driver of ES pathology in MD.