Tissue-Resident Macrophages in the Stria Vascularis

Ito, Taku; Kurata, Natsuko; Fukunaga, Yasutomo

doi:10.3389/fneur.2022.818395

Cited by 14 publications

(9 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several previous studies in rodents have shown macrophage infiltration into the stria vascularis and the subsequent development of these macrophages into PVMs ( 36 , 42 ). Observations in the present study also demonstrated that PVMs in the stria vascularis originate from infiltrating macrophages ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 91%

Distribution of macrophages in the developing cochlea of the common marmoset, a primate model animal

Hosoya,

Kitama,

Shimanuki

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

IntroductionMacrophages are essential immune cells in the cochlea that contribute to inflammation, tissue repair, and homeostasis. They also play an important role in local cochlear immunity. The developmental immigration and maturation of macrophages in the cochlea have been investigated and are considered essential for normal hearing acquisition. Most of our current knowledge regarding cochlear development is based on rodent models because of the ethical challenges of using human fetal samples for research. However, inter-species differences between rodents and humans have been reported. In this study, we used a primate animal model to investigate the distributions of macrophages in the developing cochlea. The common marmoset (Callithrix jacchus), a small monkey species that inhabits the New World, was used as the model.MethodsWe investigated the distribution of macrophages in the developing cochlea of the common marmoset by performing immunohistochemical analyses of cochlear tissue from common marmoset embryos at different development stages.ResultsWe revealed detailed distribution changes in the macrophages of a primate animal model cochlea. This observation indicates that most of the changes in the general distribution of macrophages were well preserved between rodents and this primate. The distribution changes observed in the common marmoset were also compatible with observations in the human fetus; although, observations in the human fetus are limited. Our observations in this study also revealed several differences between common marmosets and rodents.ConclusionThe time course of immunological development and maturations established in this study will aid in the study of the primate-specific developmental biology of the inner ear. These observations may eventually lead to new therapeutic strategies for hearing loss in humans. In addition, understanding the immunological steady-state of the cochlea may help in the study of age- and genetic-induced hearing loss and in the design of regenerative therapies.

show abstract

Section: Discussionmentioning

confidence: 91%

Distribution of macrophages in the developing cochlea of the common marmoset, a primate model animal

Hosoya,

Kitama,

Shimanuki

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Cochlear macrophages play an important role in homeostasis and during cochlear injury. PVMs are closely associated with the blood vessels and play a pivotal role in regulating the tight junction proteins between endothelial cells that comprise the BLB ( 34, 35 ). In noise damage models that result in the loss of hair cell synaptic ribbons, macrophages are involved in synaptic repair and the restoration of cochlear synapses and synaptic function ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Macrophage Depletion Protects Against Cisplatin-Induced Ototoxicity and Nephrotoxicity

Sung,

Hayase,

Yuen

et al. 2023

Preprint

View full text Add to dashboard Cite

Cisplatin is a widely used and highly effective anti-cancer drug with significant side effects including ototoxicity and nephrotoxicity. Macrophages, the major resident immune cells in the cochlea and kidney, are important drivers of both inflammatory and tissue repair responses. To investigate the roles of macrophages in cisplatin-induced ototoxicity and nephrotoxicity, we used PLX3397, an FDA-approved inhibitor of the colony-stimulating factor 1 receptor (CSF1R), to eliminate tissue-resident macrophages during the course of cisplatin administration. Mice treated with cisplatin alone (cisplatin/vehicle) had significant hearing loss (ototoxicity) as well as kidney injury (nephrotoxicity). Macrophage ablation using PLX3397 resulted in significantly reduced hearing loss measured by auditory brainstem responses (ABR) and distortion-product otoacoustic emissions (DPOAE). Sensory hair cells in the cochlea were protected against cisplatin-induced death in mice treated with PLX3397. Macrophage ablation also protected against cisplatin-induced nephrotoxicity, as evidenced by markedly reduced tubular injury and fibrosis as well as reduced plasma blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels. Mechanistically, our data suggest that the protective effect of macrophage ablation against cisplatin-induced ototoxicity and nephrotoxicity is mediated by reduced platinum accumulation in both the inner ear and the kidney. Together our data indicate that ablation of tissue-resident macrophages represents a novel strategy for mitigating cisplatin-induced ototoxicity and nephrotoxicity.Brief summaryMacrophage ablation using PLX3397 was protective against cisplatin-induced ototoxicity and nephrotoxicity by limiting platinum accumulation in the inner ear and kidney.

show abstract

“…Macrophages are one of the key elements of the intrinsic immune system in mature organs, and they primarily function as an immunological defense to keep the internal environment at homeostasis (Wynn and Vannella, 2016;Duan, 2018), and macrophages are resident immune cells in the cochlea (Liu et al, 2018;He et al, 2020). They play a continuous monitoring role in the homeostatic environment, thus helping maintain tissue homeostasis under pathological and physiological conditions (Ito et al, 2022). Cochlear resident macrophages exhibit remarkable plasticity, allowing them to rapidly switch between active phenotypes and adapt to changing neuronal and environmental conditions.…”

Section: Discussionmentioning

confidence: 99%

Cochlear resident macrophage mediates development of ribbon synapses via CX3CR1/CX3CL1 axis

Song

Guo

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Cochlear ribbon synapses formed between spiral ganglion neurons and inner hair cells in postnatal mice must undergo significant morphological and functional development to reach auditory maturation. However, the mechanisms underlying cochlear ribbon synapse remodeling remain unclear. This study found that cochlear resident macrophages are essential for cochlear ribbon synapse development and maturation in mice via the CX3CR1/CX3CL1 axis. CX3CR1 expression (a macrophage surface-specific receptor) and macrophage count in the cochlea were significantly increased from postnatal day 7 then decreased from days 14 to 28. Seven-day treatment with CX3CR1 inhibitors and artificial upregulation of CX3CL1 levels in the inner ear environment using the semicircular canal injection technique were initiated on day 7, and this resulted in a significant increase in hearing threshold on day 28. Additionally, abnormalities in the morphology and number of cochlear ribbon synapses were detected on day P14, which may be associated with hearing impairment. In conclusion, macrophage regulation of cochlear ribbon synapse remodeling via the CX3CR1/CX3CL1 axis is required during hearing development and offers a new perspective on immune-related hearing loss throughout auditory development. Importantly, it could be a new treatment target for sensorineural hearing loss.

show abstract

Tissue-Resident Macrophages in the Stria Vascularis

Cited by 14 publications

References 45 publications

Distribution of macrophages in the developing cochlea of the common marmoset, a primate model animal

Distribution of macrophages in the developing cochlea of the common marmoset, a primate model animal

Macrophage Depletion Protects Against Cisplatin-Induced Ototoxicity and Nephrotoxicity

Cochlear resident macrophage mediates development of ribbon synapses via CX3CR1/CX3CL1 axis

Contact Info

Product

Resources

About