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Targeting the CD4+ effector memory T cells re-expressing CD45RA suppressor galectin-7: a multi-omics-guided therapeutic strategy for idiopathic pulmonary fibrosis.

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Τίτλος: Targeting the CD4+ effector memory T cells re-expressing CD45RA suppressor galectin-7: a multi-omics-guided therapeutic strategy for idiopathic pulmonary fibrosis.
Συγγραφείς: Yan T; Department of Lung Transplantation, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, China.; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Zhongshan, 528400, China.; Jingyu Chen Lung Transplantation Laboratory, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, China., Liu J; Lung Transplantation Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China., Liu Y; Lung Transplantation Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China., Gu W; Department of Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan., Liu J; Lung Transplantation Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China., Li Y; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Zhongshan, 528400, China., Lv R; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Zhang C; Lung Transplantation Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China., Ding J; Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China., Zha C; Lung Transplantation Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China., Wang C; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Zhongshan, 528400, China. cqwang@simm.ac.cn.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. cqwang@simm.ac.cn.; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. cqwang@simm.ac.cn.; University of Chinese Academy of Sciences, Beijing, 100049, China. cqwang@simm.ac.cn., Gao F; Emergency Department, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China. gaofeimed@126.com., Huang M; Department of General Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, China. huangman@zju.edu.cn.; Key Laboratory of Multiple Organ Failure(Zhejiang University), Ministry of Education, Zhejiang, China. huangman@zju.edu.cn., Chen J; Department of Lung Transplantation, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, China. chenjy@wuxiph.com.; Lung Transplantation Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China. chenjy@wuxiph.com.; Jingyu Chen Lung Transplantation Laboratory, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, China. chenjy@wuxiph.com.; Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China. chenjy@wuxiph.com.
Πηγή: Molecular biomedicine [Mol Biomed] 2026 Oct 05; Vol. 7 (1). Date of Electronic Publication: 2026 Oct 05.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 9918283581406676 Publication Model: Electronic Cited Medium: Internet ISSN: 2662-8651 (Electronic) Linking ISSN: 26628651 NLM ISO Abbreviation: Mol Biomed Subsets: MEDLINE
Imprint Name(s): Original Publication: Singapore : Springer Singapore, [2020]-
Ιατρικοί όροι (MeSH): Leukocyte Common Antigens*/metabolism , Idiopathic Pulmonary Fibrosis*/immunology , Idiopathic Pulmonary Fibrosis*/genetics , Idiopathic Pulmonary Fibrosis*/pathology , Idiopathic Pulmonary Fibrosis*/metabolism , Galectins*/metabolism , Galectins*/genetics , CD4-Positive T-Lymphocytes*/immunology , CD4-Positive T-Lymphocytes*/metabolism , Memory T Cells*/immunology , Memory T Cells*/metabolism , Immunologic Memory*, STAT5 Transcription Factor/metabolism ; Humans ; Multiomics ; Animals ; Mice
Περίληψη: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options. Although single-cell and spatial transcriptomics have revealed cellular heterogeneity within the IPF lung microenvironment, the immune drivers with causal relevance remain poorly defined. Here, through large-scale Mendelian randomization integrating multi-omics data, we identified a consistent negative causal association between the proportion of CD4⁺ effector memory T cells re-expressing CD45RA (TEMRA) and IPF risk. Multi-platform validation-including single-cell RNA sequencing, flow cytometry, and multiplex immunofluorescence-confirmed a significant reduction in CD4⁺ TEMRA frequency in both peripheral blood and lung tissues of IPF patients, establishing this subset as a clinically relevant biomarker. Spatial transcriptomics further revealed a negative correlation between TEMRA differentiation signatures and local fibrotic burden. Mechanistically, integrated single-cell analyses pinpointed metaplastic KRT5⁺ basal cells as a key epithelial population with the capacity to disrupt immune homeostasis. These aberrant epithelial cells upregulate Galectin-7 (LGALS7), which we demonstrate competes with IL-7 for receptor binding, suppresses STAT5 phosphorylation, and limits CD4⁺ TEMRA differentiation, thereby uncovering a previously unrecognized epithelial-immune crosstalk axis in IPF. Guided by these findings, virtual screening of 20,000 compounds identified neoeriocitrin as a Galectin-7 inhibitor that restores STAT5 phosphorylation in vitro and attenuates pulmonary fibrosis in vivo. This study positions Galectin-7 as a druggable target and establishes a novel framework linking epithelial dysfunction to immune dysregulation in IPF.
(© 2026. The Author(s).)
Competing Interests: Declarations. Ethics approval and consent to participate: Studies involving human pulmonary tissue and peripheral blood samples were approved by the Nanjing Medical University (2020–374) and Wuxi People’s Hospital Research Ethics Committee (KY24162). Animal experiments were approved separately by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University (AIRB-2025–2628). Consent for publication: Not applicable. Competing of interest: The authors have declared that no conflict of interest exists.
References: Lancet Respir Med. 2025 Aug;13(8):739-755. (PMID: 40684782)
Cell Rep Methods. 2023 Jun 12;3(6):100498. (PMID: 37426759)
Nat Biotechnol. 2020 Dec;38(12):1408-1414. (PMID: 32747759)
Lung. 2013 Apr;191(2):191-8. (PMID: 23321864)
Immunity. 2023 Dec 12;56(12):2836-2854.e9. (PMID: 37963457)
Cell Rep Med. 2025 Jul 15;6(7):102209. (PMID: 40602406)
Sci Adv. 2020 Jul 08;6(28):eaba1972. (PMID: 32832598)
Am J Respir Crit Care Med. 2012 Mar 1;185(5):537-46. (PMID: 22095546)
Occup Environ Med. 2021 Feb;78(2):137-141. (PMID: 33097673)
N Engl J Med. 2025 Jun 12;392(22):2193-2202. (PMID: 40387033)
Annu Rev Immunol. 2004;22:745-63. (PMID: 15032595)
Cell Death Differ. 2023 Apr;30(4):906-921. (PMID: 36693903)
Nat Commun. 2020 Apr 21;11(1):1920. (PMID: 32317643)
J Clin Invest. 2025 Mar 18;135(10):. (PMID: 40100323)
Cancer Res. 2020 Dec 15;80(24):5583-5596. (PMID: 33093168)
Cell Death Discov. 2023 Feb 14;9(1):62. (PMID: 36788232)
Eur Respir Rev. 2025 Mar 19;34(175):. (PMID: 40107663)
Lancet Respir Med. 2021 Mar;9(3):285-294. (PMID: 33197388)
BMC Pulm Med. 2023 Oct 3;23(1):369. (PMID: 37789433)
Immunity. 2019 Dec 17;51(6):1043-1058.e4. (PMID: 31810882)
Respir Med. 2019 Feb;147:79-91. (PMID: 30704705)
Immunity. 2023 Jun 13;56(6):1285-1302.e7. (PMID: 37269830)
Nat Commun. 2017 Nov 13;8(1):1473. (PMID: 29133794)
Bioinformatics. 2019 Nov 1;35(22):4851-4853. (PMID: 31233103)
Cell Death Discov. 2017 Apr 10;3:17010. (PMID: 28417017)
Nat Genet. 2020 Oct;52(10):1036-1045. (PMID: 32929287)
Nat Genet. 2025 Mar;57(3):647-658. (PMID: 39901013)
Immunol Rev. 2023 Jul;316(1):160-175. (PMID: 37098109)
Nat Genet. 2018 May;50(5):693-698. (PMID: 29686387)
J Ethnopharmacol. 2024 Jan 30;319(Pt 2):117295. (PMID: 37806536)
Methods Mol Biol. 2022;2442:549-564. (PMID: 35320545)
Cancer Cell. 2022 Jul 11;40(7):768-786.e7. (PMID: 35750052)
JCI Insight. 2025 Feb 24;10(4):. (PMID: 39989456)
Science. 2021 Dec 17;374(6574):abe6474. (PMID: 34914499)
Am J Respir Crit Care Med. 2021 Mar 15;203(6):707-717. (PMID: 32991815)
Onco Targets Ther. 2021 Mar 25;14:2149-2161. (PMID: 33790578)
Presse Med. 2023 Sep;52(3):104166. (PMID: 37156412)
Immunity. 2022 Sep 13;55(9):1564-1580. (PMID: 36103853)
Cell Stem Cell. 2025 Sep 4;32(9):1390-1402.e9. (PMID: 40848726)
Nat Cell Biol. 2022 Jan;24(1):10-23. (PMID: 34969962)
Trends Pharmacol Sci. 2023 Aug;44(8):519-531. (PMID: 37391294)
J Clin Invest. 2023 Sep 15;133(18):. (PMID: 37712420)
Nat Genet. 2024 Aug;56(8):1725-1736. (PMID: 38951642)
Nat Commun. 2022 Sep 26;13(1):5637. (PMID: 36163190)
Nat Immunol. 2019 Dec;20(12):1584-1593. (PMID: 31745336)
J Clin Invest. 2021 Jan 19;131(2):. (PMID: 33463535)
Eur Respir J. 2022 Feb 10;59(2):. (PMID: 34172473)
World J Gastroenterol. 2016 Nov 28;22(44):9706-9717. (PMID: 27956794)
Cell. 2020 Jun 25;181(7):1612-1625.e13. (PMID: 32497499)
Thorax. 2022 Aug;77(8):829-833. (PMID: 35688625)
Nat Commun. 2025 Apr 21;16(1):3748. (PMID: 40258811)
Radiology. 2025 Jul;316(1):e242531. (PMID: 40590695)
Grant Information: 2023ZD0505900 Noncommunicable Chronic Diseases-National Science and Technology Major Project; 2023YFC2507105 National Key Research and Development Program of China; 82370070 National Natural Science Foundation of China
Contributed Indexing: Keywords: CD4+ Effector Memory T Cells Re-expressing CD45RA; Galectin-7; Idiopathic Pulmonary Fibrosis; Mendelian Randomization; Metaplastic KRT5+ Basal Cell
Substance Nomenclature: EC 3.1.3.48 (Leukocyte Common Antigens)
0 (Galectins)
0 (STAT5 Transcription Factor)
Entry Date(s): Date Created: 20261004 Date Completed: 20261005 Latest Revision: 20261007
Update Code: 20261007
PubMed Central ID: PMC13635077
DOI: 10.1186/s43556-026-00542-0
PMID: 42830359
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2662-8651
DOI:10.1186/s43556-026-00542-0