{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T12:27:03Z","timestamp":1787401623929,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304112"],"award-info":[{"award-number":["82304112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Silicosis is a work\u2010related condition resulting from breathing in crystalline silica particles, marked by persistent inflammation and abnormal healing mechanisms in the lungs. Our previous studies demonstrated that inhibition of Cxcr4 with Plerixafor (AMD3100) markedly attenuates pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      By integrating single\u2010cell RNA sequencing with spatial transcriptomics, we analysed lung tissues from a mouse model of pneumoconiosis. Using the Robust Cell Type Decomposition algorithm to deconvolve spatial transcriptomic data, we identified Cxcr4\n                      <jats:sup>+<\/jats:sup>\n                      macrophages and Cxcl12\n                      <jats:sup>+<\/jats:sup>\n                      fibroblasts as central drivers of pulmonary fibrosis progression, revealing a distinct spatial co\u2010localisation pattern between these cell populations. To further delineate macrophage heterogeneity and functional specialisation during silicosis progression, we focused on key macrophage subpopulations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AMD3100 dynamically remodels the alveolar macrophages (AMs) niche, promoting the restoration of AM homeostasis and significantly reducing both co\u2010expression and spatial co\u2010localisation of Cxcr4\/transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signalling within macrophages, thereby modulating the fibrotic immune microenvironment. Mechanistically, silica dust stimulation in vitro upregulates Cxcr4 expression in the AM cell line MH\u2010S, which in turn promotes the release of TGF\u2010\u03b2 and pro\u2010inflammatory factors, driving fibroblast activation. Activated fibroblasts further enhance the pro\u2010fibrotic phenotype of macrophages via secretion of Cxcl12, reinforcing the Cxcr4 signalling axis and establishing a stable positive\u2010feedback loop.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that silicosis\u2010associated fibrosis progresses through a positive feedback loop involving interactions between Cxcr4\n                      <jats:sup>+<\/jats:sup>\n                      AM macrophages and Cxcl12\n                      <jats:sup>+<\/jats:sup>\n                      fibroblasts. These findings highlight the therapeutic promise of targeting the Cxcl12\/Cxcr4 axis with AMD3100 as an innovative approach for silicosis treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70705","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:50:52Z","timestamp":1779947452000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010omics reveals a novel Cxcr4\n                    <sup>+<\/sup>\n                    subpopulation of alveolar macrophages and therapeutic effect of AMD3100 in mice with advanced silicosis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-0683","authenticated-orcid":false,"given":"Min","family":"Mu","sequence":"first","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"},{"name":"Key Laboratory of Industrial Dust Control and Occupational Health of the Ministry of Education Anhui University of Science and Technology  Huainan China"},{"name":"State Key Laboratory of Safe Mining of Deep Coal and Environmental Protection Huainan Mining (Group)  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1500-4173","authenticated-orcid":false,"given":"Hangbing","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjie","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical school of Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical school of Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Xie","sequence":"additional","affiliation":[{"name":"Medical school of Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Du","sequence":"additional","affiliation":[{"name":"Medical school of Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Wu","sequence":"additional","affiliation":[{"name":"Anhui Shendong Biotechnology Development Co., Ltd.  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2106-6039","authenticated-orcid":false,"given":"Xinrong","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"},{"name":"Key Laboratory of Industrial Dust Control and Occupational Health of the Ministry of Education Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Huainan China"},{"name":"Cancer Institute Fudan University Shanghai Cancer Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2025.101941"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16825"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109024"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1029085"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010025\u201001288\u20105"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010025\u201003192\u2010y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1230266"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.19.549794"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202270005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101809"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8433"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010020\u201001467\u20100"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000002448"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175981"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.20517\/and.2024.25"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2010.42.6.048"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S372751"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12989\u2010022\u201000449\u2010y"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14508"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2021.09.014"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201014\u20107"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021246\u20109"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010019\u20101874\u20101"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100619\u20100"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010021\u201000830\u2010w"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.65802"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429246636230919122745"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118744710244357231018070313"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867329666220509114232"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201022\u20101427"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010025\u201011231\u20106"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.112041"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70402"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.116899"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101781"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.131562"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl4913"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.3c03980"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201054174\u20105"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201006411\u20100"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012\u20100198OC"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151524"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz187"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06\u20102553"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.04.021"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00615\u20102024"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.137214"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1598756"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1689275"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201031368\u20105"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20180411"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.591386"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.22011"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010021\u201000775\u20109"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70705","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ctm2.70705","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70705","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:59:23Z","timestamp":1787399963000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":54,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/ctm2.70705"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70705","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"article-number":"e70705"}}