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- Title
UGRP1-modulated MARCO<sup>+</sup> alveolar macrophages contribute to age-related lung fibrosis.
- Authors
Chen, Yongyan; Hao, Xiaolei; Li, Ming; Tian, Zhigang; Cheng, Min
- Abstract
The aging lungs are vulnerable to chronic pulmonary diseases; however, the underlying mechanisms are not well understood. In this study, we compared the aging lungs of 20–24-month-old mice with the young of 10–16-week-old mice, and found that aging airway epithelial cells significantly upregulated the expression of uteroglobin-related protein 1 (UGRP1), which was responsible for the higher levels of CCL6 in the aging lungs. Alveolar macrophages (AMs) changed intrinsically with aging, exhibiting a decrease in cell number and altered gene expression. Using terminal differentiation trajectories, a population of MARCO+ AMs with the ability to produce CCL6 was identified in the aging lungs. Upregulated UGRP1was demonstrated to modulate CCL6 production of AMs in the UGRP1-MARCO pair in vivo and in vitro. Furthermore, MARCO+ AMs aggravated bleomycin-induced pulmonary fibrosis in a CCL6-dependent manner in the aged mice, and blocking MARCO or neutralizing CCL6 significantly inhibited pulmonary fibrosis, similar to the depletion of AMs. The age-related upregulation of UGRP1 and MARCO+ AMs, involved in the progression of lung fibrosis, was also observed in human lung tissues. Thus, UGRP1 modulated MARCO+ AMs regarding the age-related lung fibrosis in a CCL6-dependent manner, which is key to establishing optimal targeting for the aging population.
- Subjects
PULMONARY fibrosis; ALVEOLAR macrophages; OLDER people; LUNG diseases; EPITHELIAL cells
- Publication
Immunity & Ageing, 2023, Vol 20, Issue 1, p1
- ISSN
1742-4933
- Publication type
Article
- DOI
10.1186/s12979-023-00338-8