Time-of-day dependent trafficking and function of monocyte subsets in the cochlea

Immune cell trafficking and inflammation shows time-of-the day variations and is controlled by circadian mechanisms.

Since the cochlea possess a circadian clock and vulnerability to noise trauma varies over the day, our project aims to understand the circadian interactions between noise trauma and inflammation in the mouse cochlea.

The findings from this research will reveal novel circadian-dependent immune mechanisms that impair hearing and which will serve as a basis for establishing new chronopharmacological approaches for preventing and or treating from noise-induced hearing loss.This proposal will offer the first detailed molecular characterization of monocyte subsets and their properties in basal and noise challenged conditions over the course of the day.

We will determine the monocyte subset displaying circadian rhythmicity in the cochlea, responsible for impairing auditory recovery.

Given the increasing value of chronopharmacological approaches for improving treatment efficacy and decrease side-effects, the fundamental knowledge deriving from this project will propose a new time-adjusted blockade of chemokines to prevent the exacerbation of noise damage, which is a major public health issue.

The main methods to be employed in this study go beyond the immunocytochemical techniques that are commonly used in the auditory field for assessing immune responses. Here, we will be employing technologies such as single-cell RNAseq, FACS, cytokine multiplex assays and RNAscope.