ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Cochlear macrophage CD74 enhances the apoptosis of senescent cochlear hair cells by down-regulating MIF
1. The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
2. Sun Yat-Sen University, Guangzhou, China
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Abstract
Age-related hearing loss is a global public health issue that impacts the quality of life in the elderly population. Macrophages are the main immune cell population in the cochlea, yet the role in the development and progression of age-related hearing loss is still unclear. This study analyzed single-cell sequencing data from cochlear tissues of C57BL/6J mice across different ages and identified notable increase in CD74 expression in macrophages with aging. Validation revealed that CD74 levels were elevated in the aged cochlea, while macrophage migration inhibitory factor (MIF) levels decreased. MIF was significantly reduced in both senescent HEI-OC1 cells and supernatant. Notably, the senescent HEI-OC1 supernatant stimulated BV2 cells CD74 expression increased. rCD74 significantly upregulated apoptosis-related genes expression levels in HEI-OC1 cells, while decreasing MIF levels. In the co-culture system of scrambled/CD74-BV2 cells and HEI-OC1 cells, CD74-BV2 cells markedly reduced the apoptosis-related genes expression in senescent HEI-OC1 cells. MIF could improve the mitochondrial membrane potential of both groups of HEI-OC1 cells, and decreased the TUNEL positive cells significantly. Our findings using the HEI-OC1 cell model reveal that macrophages secrete CD74 into the microenvironment, where it interacts with MIF, reducing local MIF levels. This interaction weakens MIF's protective effect on senescent HEI-OC1 cells, promoting apoptosis in these auditory cells. This suggests a potential mechanism whereby elevated CD74 in the aging cochlear microenvironment may contribute to the loss of hair cells in vivo. Targeting macrophage CD74 may offer therapeutic potential for preventing and treating age-related hearing loss.
Summary
Keywords
age-related hearing loss, CD74, Hair cells, Macrophages, MIF
Received
21 November 2025
Accepted
18 February 2026
Copyright
© 2026 Sun, Sun, Zhao, Wen and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xiao Mei Sun; Weiping Wen; Fanqin Wei
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