The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression

Nordström, Charlotta Kämpfe; Danckwardt-Lillieström, Niklas; Laurell, Göran; Liu, Wei; Rask‐Andersen, Helge

doi:10.3389/fimmu.2018.03181

Cited by 49 publications

(41 citation statements)

References 67 publications

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“…Immune responsiveness in the inner ear was firstly associated to the ES (14–16), however the presence of immune capacity in the cochlea has since been determined (17), namely due to the recent demonstration of IBA1 cells in the human ES and cochlea that express Major Histocompatibility Complex Type II (MHCII) (18). Nordström et al (18) identified that the macrophage population of the stria vascularis, spiral ligament and spiral ganglion expressed MHCII, which is essential to initiate antigen-specific immune responses. Moreover, they propose that there might be an uptake and processing of antigens from the ES lumen, due to the co-expression of IBA1 and MHCII in epithelial cells and to trans-epithelial migration.…”

Section: Discussionmentioning

confidence: 99%

Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease

et al. 2019

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Vestibular Migraine (VM) and Meniere's Disease (MD) are episodic vestibular syndromes defined by a set of associated symptoms such as tinnitus, hearing loss or migraine features during the attacks. Both conditions may show symptom overlap and there is no biological marker to distinguish them. Two subgroups of MD patients have been reported, according to their IL-1β profile. Therefore, considering the clinical similarity between VM and MD, we aimed to investigate the cytokine profile of MD and VM as a means to distinguish these patients. We have also carried out gene expression microarrays and measured the levels of 14 cytokines and 11 chemokines in 129 MD patients, 82 VM patients, and 66 healthy controls. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in MD patients with high and low basal levels of IL- 1β and VM patients. MD patients with high basal levels of IL- 1β (MDH) had overall higher levels of cytokines/chemokines when compared to the other subsets. CCL4 levels were significantly different between MDH, MD with low basal levels of IL- 1β (MDL), VM and controls. Logistic regression identified IL- 1β, CCL3, CCL22, and CXCL1 levels as capable of differentiating VM patients from MD patients (area under the curve = 0.995), suggesting a high diagnostic value in patients with symptoms overlap.

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Section: Discussionmentioning

confidence: 99%

Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease

et al. 2019

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“…New microscopic techniques have increased our concept of the molecular organization of the human inner ear. Immunohistochemistry was performed using super-resolution structured illumination microscopy (SR-SIM) of well-fixed specimens after mild decalcification (10–12). The ion channel machinery of the lateral wall (“cochlear battery”) was recently analyzed (10, 13).…”

Section: Introductionmentioning

confidence: 99%

“…The ion channel machinery of the lateral wall (“cochlear battery”) was recently analyzed (10, 13). Immune localization of IBA1-positive macrophages was made in the cochlea and ES (12, 14). This verified the existence of a multitude of macrophages in the human inner ear as previously demonstrated by light microscopy and immunostaining of celloidin sections of temporal bones (15).…”

Section: Introductionmentioning

confidence: 99%

“…This verified the existence of a multitude of macrophages in the human inner ear as previously demonstrated by light microscopy and immunostaining of celloidin sections of temporal bones (15). Here, we extended the analysis of the human ES, cochlea, and cochlear and vestibular nerves and ganglia (12, 14). We further analyzed CD4 and CD8 lymphocytes in the cochlea (16) and the ES.…”

Section: Introductionmentioning

confidence: 99%

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Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study

Liu

Nordström

Danckwardt-Lillieström

et al. 2019

Front. Neurol.

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Background: Like the brain, the human inner ear was long thought to be devoid of immune activity. Only the endolymphatic sac (ES) was known to be endowed with white blood cells that could process antigens and serve as an immunologic defense organ for the entire inner ear. Unexpectedly, the cochlear and vestibular organs, including the eighth cranial nerve, were recently shown to contain macrophages whose functions and implication in ear disease are somewhat undefined. Here, we review recent inner ear findings in man and extend the analyses to the vestibular nerve using super-resolution structured illumination microscopy (SR-SIM). Materials and Methods: Human ESs and cochleae were collected during surgery to treat patients with vestibular schwannoma and life-threatening petro-clival meningioma compressing the brainstem. The ESs and cochleae were placed in fixative, decalcified, and rapidly frozen and cryostat sectioned. Antibodies against ionized calcium-binding adaptor molecule 1-expressing cells (IBA1 cells), laminin β2 and type IV collagen TUJ1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), CD68, CD11b, CD4, CD8, the major histocompatibility complex type II (MHCII), and the microglial marker TEME119 were used. Results: IBA1-positive cells were present in the ESs, the cochlea, central and peripheral axons of the cochlear nerve, and the vestibular nerve trunk. IBA1 cells were found in the cochlear lateral wall, spiral limbus, and spiral ganglion. Notable variants of IBA1 cells adhered to neurons with “synapse-like” specializations and cytoplasmic projections. Slender IBA1 cells occasionally protracted into the basal lamina of the Schwann cells and had intimate contact with surrounding axons. Discussion: The human eighth nerve may be under the control of a well-developed macrophage cell system. A small number of CD4+ and CD8+ cells were found in the ES and occasionally in the cochlea, mostly located in the peripheral region of Rosenthal's canal. A neuro-immunologic axis may exist in the human inner ear that could play a role in the protection of the auditory nerve. The implication of the macrophage system during disease, surgical interventions, and cell-based transplantation should be further explored.

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“…The technique used to collect the ES was recently described by the authors (Kämpfe Nordström et al 2018). After obtaining ethical permission, human ESs were collected during trans-labyrinthine vestibular schwannoma removal.…”

Section: The Human Vestibular Aqueductmentioning

confidence: 99%

“Reversed polarization” of Na/K-ATPase—a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study

Nordström

Danckwardt-Lillieström

Liu

et al. 2019

Cell Tissue Res

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The human endolymphatic sac (ES) is believed to regulate inner ear fluid homeostasis and to be associated with Meniere's disease (MD). We analyzed the ion transport protein sodium/potassium-ATPase (Na/K-ATPase) and its isoforms in the human ES using super-resolution structured illumination microscopy (SR-SIM). Human vestibular aqueducts were collected during translabyrinthine vestibular schwannoma surgery after obtaining ethical permission. Antibodies against various isoforms of Na/K-ATPase and additional solute-transporting proteins, believed to be essential for ion and fluid transport, were used for immunohistochemistry. A population of epithelial cells of the human ES strongly expressed Na/K-ATPase α1, β1, and β3 subunit isoforms in either the lateral/basolateral or apical plasma membrane domains. The β1 isoform was expressed in the lateral/ basolateral plasma membranes in mostly large cylindrical cells, while β3 and α1 both were expressed with "reversed polarity" in the apical cell membrane in lower epithelial cells. The heterogeneous expression of Na/K-ATPase subunits substantiates earlier notions that the ES is a dynamic structure where epithelial cells show inverted epithelial transport. Dual absorption and secretion processes may regulate and maintain inner ear fluid homeostasis. These findings may shed new light on the etiology of endolymphatic hydrops and MD.

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The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression

Cited by 49 publications

References 67 publications

Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease

Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease

Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study

“Reversed polarization” of Na/K-ATPase—a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study

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