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Cochlear macrophage CD74 enhances the apoptosis of senescent cochlear hair cells by down-regulating MIF

Xiao-Mei Sun1,2, Qi-Yang Sun1,2, Meng-Qi Zhao1,2

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Frontiers in Immunology
|March 26, 2026
PubMed

Insights

Macrophages in aging ears increase CD74, a protein that reduces protective MIF levels. This leads to auditory cell apoptosis, contributing to age-related hearing loss and suggesting CD74 as a therapeutic target.

Area of Science:

  • Otolaryngology
  • Immunology
  • Cell Biology

Background:

  • Age-related hearing loss (presbycusis) significantly impacts the elderly population globally.
  • Macrophages are the primary immune cells in the cochlea, but their role in age-related hearing loss is not fully understood.
  • Understanding cochlear immune cell function is crucial for addressing hearing impairment in aging individuals.

Purpose of the Study:

  • To investigate the role of macrophage CD74 expression in the aging cochlea.
  • To elucidate the molecular mechanism linking macrophage activity to age-related hearing loss.
  • To identify potential therapeutic targets for preserving hearing in the elderly.

Main Methods:

  • Single-cell sequencing of cochlear tissues from C57BL/6J mice at different ages.
  • Validation of CD74 and macrophage migration inhibitory factor (MIF) levels in aged cochleae.
  • In vitro studies using HEI-OC1 and BV2 cell lines to model senescence and macrophage interaction.
  • Co-culture experiments to assess the impact of CD74-deficient macrophages on senescent cells.
  • Mitochondrial membrane potential and apoptosis assays (TUNEL staining).

Main Results:

  • CD74 expression in cochlear macrophages significantly increases with age.
  • Elevated CD74 in the aging cochlea correlates with decreased MIF levels.
  • Macrophage-derived CD74 reduces MIF levels and impairs its protective effects on senescent auditory cells, promoting apoptosis.
  • Targeting CD74 on macrophages reduced apoptosis in senescent HEI-OC1 cells.

Conclusions:

  • Macrophage CD74 plays a critical role in age-related hearing loss by modulating MIF levels and promoting auditory cell apoptosis.
  • The interaction between CD74 and MIF in the cochlear microenvironment represents a key mechanism contributing to hair cell loss.
  • Targeting macrophage CD74 presents a promising therapeutic strategy for preventing and treating age-related hearing loss.
Keywords:
CD74MIFage-related hearing losshair cellsmacrophages

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