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Nature Communications Mar 2023Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in...
Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1β production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis.
Topics: Animals; Mice; Meniere Disease; Glucocorticoids; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Endolymphatic Hydrops; Macrophages
PubMed: 36872329
DOI: 10.1038/s41467-023-36949-4 -
Clinical and Experimental... Feb 2022Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of... (Review)
Review
Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evidence to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.
PubMed: 35124944
DOI: 10.21053/ceo.2021.00920 -
Clinical Immunology (Orlando, Fla.) Jul 2023Meniere Disease (MD) is an inner ear syndrome, characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. The pathological mechanism...
BACKGROUND
Meniere Disease (MD) is an inner ear syndrome, characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. The pathological mechanism leading to sporadic MD is still poorly understood, however an allergic inflammatory response seems to be involved in some patients with MD.
OBJECTIVE
Decipher an immune signature associated with the syndrome.
METHODS
We performed mass cytometry immune profiling on peripheral blood from MD patients and controls. We analyzed differences in state and differences in abundance of the different cellular subsets. IgE levels were quantified through ELISA on supernatant of cultured whole blood.
RESULTS
We have identified two clusters of individuals according to the single cell cytokine profile. These clusters presented differences in IgE levels, immune cell population abundance, including a reduction of CD56 NK-cells, and changes in cytokine expression with a different response to bacterial and fungal antigens.
CONCLUSION
Our results support a systemic inflammatory response in some MD patients that show a type 2 response with allergic phenotype, which could benefit from personalized IL-4 blockers.
Topics: Humans; Meniere Disease; Vertigo; Cytokines; Hearing Loss, Sensorineural; Syndrome; Immunoglobulin E
PubMed: 37178857
DOI: 10.1016/j.clim.2023.109632 -
Ugeskrift For Laeger Apr 2021Dizziness and vertigo are frequent symptoms in the primary care facility and emergency departments. Episodic vestibular syndrome (EVS) is defined as episodic dizziness,... (Review)
Review
Dizziness and vertigo are frequent symptoms in the primary care facility and emergency departments. Episodic vestibular syndrome (EVS) is defined as episodic dizziness, vertigo or postural imbalance with remission between episodes. EVS can be divided into spontaneous (s-EVS) and triggered EVS (t-EVS). Causes of s-EVS are vestibular migraine, Menière's disease, transient ischaemic attack and vestibular paroxysmia. Causes of t-EVS are benign paroxysmal positionel vertigo, orthostatic hypotension and panick attacks. In this review, we recommend using vestibular syndromes in order to reduce the number of differential diagnoses.
Topics: Benign Paroxysmal Positional Vertigo; Dizziness; Humans; Meniere Disease; Migraine Disorders; Vestibular Diseases
PubMed: 33913418
DOI: No ID Found -
Frontiers in Surgery 2022
PubMed: 35574539
DOI: 10.3389/fsurg.2022.913741