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Current treatments remain largely ineffective due to an incomplete understanding of the complex pathology, including the interactions between fibroblasts and profibrotic immune cells within fibrotic lungs. To elucidate the dynamics of fibrosis, we performed single-cell RNA sequencing on bronchoalveolar lavage fluid obtained from patients with interstitial lung disease (ILD). We identified the SPP1- and APOE-expressing macrophage population that is commonly present across ILDs. Histological analysis showed that this macrophage population accumulated at the center of fibrotic foci. Furthermore, the ratio of this macrophage population was increased in both progressive pulmonary fibrosis and idiopathic pulmonary fibrosis. Transcriptomic analysis further divided this macrophage population into two subsets: SLC40A1\u207a or HAMP\u207a fibrosis-associated macrophages. We found that the relative balance of IL-10 and IL-8 regulated SLC40A1 and HAMP expression within fibrosis-associated macrophages. Additionally, histological analysis revealed that bronchial epithelium expressed IL-8, while type II alveolar epithelial cells expressed IL-10 in the fibrotic lung. SLC40A1\u207a fibrosis-associated macrophages localized to CD31\u207a perivascular regions and mediated the uptake and degradation of the hemoglobin\u2013haptoglobin complex. This dual pathway\u2014providing iron via SLC40A1 and intracellular iron accumulation via HAMP\u2014facilitated the transition of fibroblasts into SPP1\u207a myofibroblasts. Moreover, ferroptotic fibroblasts secreted transforming growth factor-beta 1 (TGF-\u03b21), which further contributes to fibrotic progression. In conclusion, aberrant iron metabolism orchestrated by fibrosis-associated macrophages may contribute to fibrosis by facilitating the transition of myofibroblasts. These findings provide mechanistic insight into the progression of autonomous pulmonary fibrosis.<\/jats:p>","DOI":"10.1093\/intimm\/dxag017","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:53:19Z","timestamp":1776858799000},"page":"521-534","source":"Crossref","is-referenced-by-count":0,"title":["Distinct fibrosis-associated macrophage subsets coordinate iron metabolism in pulmonary fibrosis"],"prefix":"10.1093","volume":"38","author":[{"given":"Hiroshi","family":"Nabeshima","sequence":"first","affiliation":[{"name":"Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center (WPI-IFReC), Osaka University , Osaka 565-0871 ,","place":["Japan"]},{"name":"Department of Immunology, Osaka Research Center for Drug Discovery, Otsuka Pharmaceutical Co. 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