{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:20:17Z","timestamp":1793827217379,"version":"4.6.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Mesenchymal stromal cell (MSC) transplantation has achieved significant clinical benefits for many diseases, such as systemic lupus erythematosus (SLE) and inflammatory diseases. However, the detailed therapeutic mechanism of MSCs is not fully understood. Here, in the SLE treatment, we show that MSC transplantation triggers recipient bone marrow neutrophil aggregation to generate an endogenous extracellular vesicle (EV) storm in the circulation via the TNF\u03b1\/ICAM-1\/Rab11b axis. Interestingly, blockade of the EV storm abolishes the MSC-mediated therapeutic effect for SLE. The level of EV storm is positively associated with the therapeutic effect of MSCs in SLE patients. Mechanistically, aggregated neutrophils-derived EV storms equalize Th17 and T-regulatory (Treg) cells to promote immune tolerance and disease remission <jats:italic>via<\/jats:italic> the DHA\/LILRB4\/STAT5\/STAT3 pathway in the MSC treatment for SLE. Taken together, our findings reveal a new immune-modulating function of MSCs through the induction of endogenous neutrophil aggregation in the bone marrow, which results in the secretion of EV storms for immune tolerance in SLE mice and patients. In addition, this study revealed a previously unknown role of the recipient EV storm in determining the therapeutic effect of MSC in SLE, and the recipient EV storm can be used to predict the therapeutic efficacy of MSCs in SLE therapy.<\/jats:p>","DOI":"10.1038\/s41392-025-02442-1","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T05:00:55Z","timestamp":1760331655000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mesenchymal stromal cells induce neutrophil aggregation and extracellular vesicle storms for systemic lupus erythematosus"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-1851","authenticated-orcid":false,"given":"Qianmin","family":"Ou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhan","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genhong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhui","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zetao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3409-5012","authenticated-orcid":false,"given":"Andy Peng","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1516-7500","authenticated-orcid":false,"given":"Songtao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"2442_CR1","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/s41409-025-02531-3","volume":"60","author":"L Daenen","year":"2025","unstructured":"Daenen, L. et al. The use of MSCs in steroid-refractory acute GvHD in Europe: a survey from the EBMT cellular therapy & immunobiology working party. Bone Marrow Transpl. 60, 708\u2013714 (2025).","journal-title":"Bone Marrow Transpl."},{"key":"2442_CR2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13287-025-04184-x","volume":"16","author":"L Zeng","year":"2025","unstructured":"Zeng, L. et al. Efficacy and safety of mesenchymal stromal cell transplantation in the treatment of autoimmune and rheumatic immune diseases: a systematic review and meta-analysis of randomized controlled trials. Stem Cell Res. Ther. 16, 65 (2025).","journal-title":"Stem Cell Res. Ther."},{"key":"2442_CR3","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13287-024-03707-2","volume":"15","author":"Y Zhu","year":"2024","unstructured":"Zhu, Y. et al. Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I\/II randomized, double-blind, placebo-controlled study. Stem Cell Res. Ther. 15, 122 (2024).","journal-title":"Stem Cell Res. Ther."},{"key":"2442_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-024-08128-3","volume":"25","author":"NT Nguyen","year":"2024","unstructured":"Nguyen, N. T. et al. Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial. Trials 25, 309 (2024).","journal-title":"Trials"},{"key":"2442_CR5","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1016\/j.stem.2021.09.006","volume":"28","author":"M Krampera","year":"2021","unstructured":"Krampera, M. & Le Blanc, K. Mesenchymal stromal cells: putative microenvironmental modulators become cell therapy. Cell Stem Cell 28, 1708\u20131725 (2021).","journal-title":"Cell Stem Cell"},{"key":"2442_CR6","doi-asserted-by":"crossref","unstructured":"Galleu, A. et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci. Transl. Med. 9, eaam7828 (2017).","DOI":"10.1126\/scitranslmed.aam7828"},{"key":"2442_CR7","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/s41423-023-01018-9","volume":"20","author":"C Giacomini","year":"2023","unstructured":"Giacomini, C., Graneli, C., Hicks, R. & Dazzi, F. The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair. Cell Mol. Immunol. 20, 570\u2013582 (2023).","journal-title":"Cell Mol. Immunol."},{"key":"2442_CR8","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jcyt.2025.01.005","volume":"27","author":"KL Blanc","year":"2025","unstructured":"Blanc, K. L. et al. ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells. Cytotherapy 27, 413\u2013416 (2025).","journal-title":"Cytotherapy"},{"key":"2442_CR9","doi-asserted-by":"publisher","first-page":"21","DOI":"10.4049\/jimmunol.174.1.21","volume":"174","author":"T Cupedo","year":"2005","unstructured":"Cupedo, T. & Mebius, R. E. Cellular interactions in lymph node development. J. Immunol. 174, 21\u201325 (2005).","journal-title":"J. Immunol."},{"key":"2442_CR10","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1242\/dev.135400","volume":"143","author":"KD Walton","year":"2016","unstructured":"Walton, K. D. et al. Villification in the mouse: Bmp signals control intestinal villus patterning. Development 143, 427\u2013436 (2016).","journal-title":"Development"},{"key":"2442_CR11","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1016\/j.cell.2021.02.034","volume":"184","author":"M Levin","year":"2021","unstructured":"Levin, M. Bioelectric signaling: reprogrammable circuits underlying embryogenesis, regeneration, and cancer. Cell 184, 1971\u20131989 (2021).","journal-title":"Cell"},{"key":"2442_CR12","doi-asserted-by":"publisher","first-page":"4155","DOI":"10.1016\/j.cub.2020.08.006","volume":"30","author":"JT Pentz","year":"2020","unstructured":"Pentz, J. T. et al. Ecological advantages and evolutionary limitations of aggregative multicellular development. Curr. Biol. 30, 4155\u20134164.e6 (2020).","journal-title":"Curr. Biol."},{"key":"2442_CR13","doi-asserted-by":"publisher","first-page":"4546","DOI":"10.1016\/j.cell.2023.08.043","volume":"186","author":"RR Maas","year":"2023","unstructured":"Maas, R. R. et al. The local microenvironment drives activation of neutrophils in human brain tumors. Cell 186, 4546\u20134566.e27 (2023).","journal-title":"Cell"},{"key":"2442_CR14","doi-asserted-by":"publisher","first-page":"3690","DOI":"10.1016\/j.cell.2024.05.003","volume":"187","author":"H Wang","year":"2024","unstructured":"Wang, H. et al. Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss. Cell 187, 3690\u20133711.e19 (2024).","journal-title":"Cell"},{"key":"2442_CR15","doi-asserted-by":"publisher","first-page":"107655","DOI":"10.1016\/j.isci.2023.107655","volume":"26","author":"L Brown","year":"2023","unstructured":"Brown, L. & Yipp, B. G. Neutrophil swarming: is a good offense the best defense?. iScience 26, 107655 (2023).","journal-title":"iScience"},{"key":"2442_CR16","doi-asserted-by":"crossref","unstructured":"Kienle, K. et al. Neutrophils self-limit swarming to contain bacterial growth in vivo. Science 372, eabe7729 (2021).","DOI":"10.1126\/science.abe7729"},{"key":"2442_CR17","doi-asserted-by":"crossref","unstructured":"Inamo, J. et al. Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis. J. Clin. Investig. 135, e185217 (2025).","DOI":"10.1172\/JCI185217"},{"key":"2442_CR18","doi-asserted-by":"publisher","first-page":"4168","DOI":"10.1016\/j.cell.2021.05.045","volume":"184","author":"A Wagner","year":"2021","unstructured":"Wagner, A. et al. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 184, 4168\u20134185.e21 (2021).","journal-title":"Cell"},{"key":"2442_CR19","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1038\/jid.2014.488","volume":"135","author":"SC Han","year":"2015","unstructured":"Han, S. C. et al. Docosahexaenoic acid alleviates atopic dermatitis by generating tregs and IL-10\/TGF-beta-modified macrophages via a TGF-beta-dependentmechanism. J. Investig. Dermatol. 135, 1556\u20131564 (2015).","journal-title":"J. Investig. Dermatol."},{"key":"2442_CR20","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1158\/2326-6066.CIR-23-0359","volume":"12","author":"S Wu","year":"2024","unstructured":"Wu, S. et al. The omega-3 polyunsaturated fatty acid docosahexaenoic acid enhances NK-Cell antitumor effector functions. Cancer Immunol. Res. 12, 744\u2013758 (2024).","journal-title":"Cancer Immunol. Res."},{"key":"2442_CR21","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41423-019-0321-2","volume":"17","author":"Z Li","year":"2020","unstructured":"Li, Z. et al. LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells. Cell Mol. Immunol. 17, 272\u2013282 (2020).","journal-title":"Cell Mol. Immunol."},{"key":"2442_CR22","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41586-018-0615-z","volume":"562","author":"M Deng","year":"2018","unstructured":"Deng, M. et al. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature 562, 605\u2013609 (2018).","journal-title":"Nature"},{"key":"2442_CR23","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41586-024-07752-y","volume":"632","author":"H Sultan","year":"2024","unstructured":"Sultan, H. et al. Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy. Nature 632, 182\u2013191 (2024).","journal-title":"Nature"},{"key":"2442_CR24","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1093\/intimm\/dxz017","volume":"31","author":"YL Wong","year":"2019","unstructured":"Wong, Y. L. et al. Gp49B is a pathogenic marker for auto-antibody-producing plasma cells in lupus-prone BXSB\/Yaa mice. Int. Immunol. 31, 397\u2013406 (2019).","journal-title":"Int. Immunol."},{"key":"2442_CR25","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.cmet.2017.12.001","volume":"27","author":"M Whitham","year":"2018","unstructured":"Whitham, M. et al. Extracellular vesicles provide a means for tissue crosstalk during exercise. Cell Metab. 27, 237\u2013251.e4 (2018).","journal-title":"Cell Metab."},{"key":"2442_CR26","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.cell.2018.09.005","volume":"175","author":"C Crewe","year":"2018","unstructured":"Crewe, C. et al. An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state. Cell 175, 695\u2013708.e13 (2018).","journal-title":"Cell"},{"key":"2442_CR27","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1080\/08820139.2022.2055478","volume":"51","author":"W Sun","year":"2022","unstructured":"Sun, W. et al. Mesenchymal stem cells-derived exosomes ameliorate lupus by inducing m2 macrophage polarization and regulatory T cell expansion in MRL\/lpr mice. Immunol. Investig. 51, 1785\u20131803 (2022).","journal-title":"Immunol. Investig."},{"key":"2442_CR28","doi-asserted-by":"publisher","first-page":"1355845","DOI":"10.3389\/fimmu.2024.1355845","volume":"15","author":"C Wong","year":"2024","unstructured":"Wong, C., Stoilova, I., Gazeau, F., Herbeuval, J. P. & Fourniols, T. Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE. Front. Immunol. 15, 1355845 (2024).","journal-title":"Front. Immunol."},{"key":"2442_CR29","doi-asserted-by":"crossref","unstructured":"Olofsen, P. A. et al. Effective, long-term, neutrophil depletion using a murinized anti-Ly-6G 1A8 antibody. Cells 11,3406 (2022).","DOI":"10.3390\/cells11213406"},{"key":"2442_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0022-1759(89)90178-6","volume":"124","author":"N Van Rooijen","year":"1989","unstructured":"Van Rooijen, N. The liposome-mediated macrophage \u2018suicide\u2019 technique. J. Immunol. Methods 124, 1\u20136 (1989).","journal-title":"J. Immunol. Methods"},{"key":"2442_CR31","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1016\/j.cell.2018.11.012","volume":"175","author":"WC Peng","year":"2018","unstructured":"Peng, W. C. et al. Inflammatory cytokine TNFalpha promotes the long-term expansion of primary hepatocytes in 3D culture. Cell 175, 1607\u20131619.e15 (2018).","journal-title":"Cell"},{"key":"2442_CR32","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.4049\/jimmunol.2100512","volume":"207","author":"MH Kaaij","year":"2021","unstructured":"Kaaij, M. H. et al. Overexpression of transmembrane tnf drives development of ectopic lymphoid structures in the bone marrow and B cell lineage alterations in experimental spondyloarthritis. J. Immunol. 207, 2337\u20132346 (2021).","journal-title":"J. Immunol."},{"key":"2442_CR33","doi-asserted-by":"crossref","unstructured":"Tixi, W. et al. Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation. Elife 12,e90006 (2023).","DOI":"10.7554\/eLife.90006"},{"key":"2442_CR34","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.cell.2014.09.051","volume":"159","author":"MC Boelens","year":"2014","unstructured":"Boelens, M. C. et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell 159, 499\u2013513 (2014).","journal-title":"Cell"},{"key":"2442_CR35","doi-asserted-by":"crossref","unstructured":"Kalluri, R. & LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science 367,eaau6977 (2020).","DOI":"10.1126\/science.aau6977"},{"key":"2442_CR36","doi-asserted-by":"crossref","unstructured":"Brunel, A. et al. Autophagy and extracellular vesicles, connected to rabgtpase family, support aggressiveness in cancer stem cells. Clls. 10,1330 (2021).","DOI":"10.3390\/cells10061330"},{"key":"2442_CR37","doi-asserted-by":"crossref","unstructured":"Harrison, M. C. & Lai, P. K. Investigating the mechanisms of antibody binding to alpha-synuclein for the Treatment of Parkinson\u2019s disease. Mol Pharm. 21, 5326\u20135334 (2024).","DOI":"10.1021\/acs.molpharmaceut.4c00879"},{"key":"2442_CR38","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s44342-024-00007-2","volume":"22","author":"AS Roy","year":"2024","unstructured":"Roy, A. S. et al. A computational approach for structural and functional analyses of disease-associated mutations in the human CYLD gene. Genom. Inf. 22, 4 (2024).","journal-title":"Genom. Inf."},{"key":"2442_CR39","doi-asserted-by":"publisher","first-page":"e208","DOI":"10.1016\/S2665-9913(19)30076-1","volume":"1","author":"RA Furie","year":"2019","unstructured":"Furie, R. A. et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 1, e208\u2013e219 (2019).","journal-title":"Lancet Rheumatol."},{"key":"2442_CR40","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1093\/intimm\/dxw044","volume":"28","author":"M Inui","year":"2016","unstructured":"Inui, M. et al. Tolerogenic immunoreceptor ILT3\/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE. Int. Immunol. 28, 597\u2013604 (2016).","journal-title":"Int. Immunol."},{"key":"2442_CR41","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1007\/s11033-021-07079-1","volume":"49","author":"CZ Wang","year":"2022","unstructured":"Wang, C. Z. et al. Effects of dihydroartemisinin, a metabolite of artemisinin, on colon cancer chemoprevention and adaptive immune regulation. Mol. Biol. Rep. 49, 2695\u20132709 (2022).","journal-title":"Mol. Biol. Rep."},{"key":"2442_CR42","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41551-018-0325-8","volume":"3","author":"JQ Yin","year":"2019","unstructured":"Yin, J. Q., Zhu, J. & Ankrum, J. A. Manufacturing of primed mesenchymal stromal cells for therapy. Nat. Biomed. Eng. 3, 90\u2013104 (2019).","journal-title":"Nat. Biomed. Eng."},{"key":"2442_CR43","doi-asserted-by":"crossref","unstructured":"Borkowska, P., Morys, J., Zielinska, A., Sadlocha, M. & Kowalski, J. Survival and neurogenesis-promoting effects of the co-overexpression of BCLXL and BDNF genes on Wharton\u2019s Jelly-Derived mesenchymal stem cells. Life 12,1406 (2022).","DOI":"10.3390\/life12091406"},{"key":"2442_CR44","doi-asserted-by":"crossref","unstructured":"Dunn, C. M. et al. Interferon-gamma primed human clonal mesenchymal stromal cell sheets exhibit enhanced immunosuppressive function. Cells 11, 3738 (2022).","DOI":"10.3390\/cells11233738"},{"key":"2442_CR45","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1002\/eji.200838433","volume":"38","author":"F Dazzi","year":"2008","unstructured":"Dazzi, F. & Marelli-Berg, F. M. Mesenchymal stem cells for graft-versus-host disease: close encounters with T cells. Eur. J. Immunol. 38, 1479\u20131482 (2008).","journal-title":"Eur. J. Immunol."},{"key":"2442_CR46","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1016\/j.ymthe.2023.10.004","volume":"31","author":"TS Cheung","year":"2023","unstructured":"Cheung, T. S. et al. Apoptosis in mesenchymal stromal cells activates an immunosuppressive secretome predicting clinical response in Crohn\u2019s disease. Mol. Ther. 31, 3531\u20133544 (2023).","journal-title":"Mol. Ther."},{"key":"2442_CR47","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","volume":"383","author":"DC Fajgenbaum","year":"2020","unstructured":"Fajgenbaum, D. C. & June, C. H. Cytokine Storm. N. Engl. J. Med. 383, 2255\u20132273 (2020).","journal-title":"N. Engl. J. Med."},{"key":"2442_CR48","doi-asserted-by":"publisher","first-page":"5500","DOI":"10.1016\/j.cell.2023.10.025","volume":"186","author":"D Sang","year":"2023","unstructured":"Sang, D. et al. Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals. Cell 186, 5500\u20135516.e21 (2023).","journal-title":"Cell"},{"key":"2442_CR49","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41577-022-00763-8","volume":"23","author":"EI Buzas","year":"2023","unstructured":"Buzas, E. I. The roles of extracellular vesicles in the immune system. Nat. Rev. Immunol. 23, 236\u2013250 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"2442_CR50","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/jor.23258","volume":"35","author":"E Aktas","year":"2017","unstructured":"Aktas, E. et al. Immune modulation with primed mesenchymal stem cells delivered via biodegradable scaffold to repair an Achilles tendon segmental defect. J. Orthop. Res. 35, 269\u2013280 (2017).","journal-title":"J. Orthop. Res."},{"key":"2442_CR51","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.ymthe.2017.12.013","volume":"26","author":"L Boland","year":"2018","unstructured":"Boland, L. et al. IFN-gamma and TNF-alpha pre-licensing protects mesenchymal stromal cells from the pro-inflammatory effects of palmitate. Mol. Ther. 26, 860\u2013873 (2018).","journal-title":"Mol. Ther."},{"key":"2442_CR52","doi-asserted-by":"publisher","first-page":"945234","DOI":"10.3389\/fimmu.2022.945234","volume":"13","author":"J Li","year":"2022","unstructured":"Li, J. et al. Tumor necrosis factor-alpha-primed mesenchymal stem cell-derived exosomes promote M2 macrophage polarization via Galectin-1 and modify intrauterine adhesion on a novel murine model. Front. Immunol. 13, 945234 (2022).","journal-title":"Front. Immunol."},{"key":"2442_CR53","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/imr.12458","volume":"273","author":"K Kienle","year":"2016","unstructured":"Kienle, K. & Lammermann, T. Neutrophil swarming: an essential process of the neutrophil tissue response. Immunol. Rev. 273, 76\u201393 (2016).","journal-title":"Immunol. Rev."},{"key":"2442_CR54","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nature12175","volume":"498","author":"T Lammermann","year":"2013","unstructured":"Lammermann, T. et al. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature 498, 371\u2013375 (2013).","journal-title":"Nature"},{"key":"2442_CR55","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1016\/j.cub.2020.05.030","volume":"30","author":"H Poplimont","year":"2020","unstructured":"Poplimont, H. et al. Neutrophil swarming in damaged tissue is orchestrated by connexins and cooperative calcium alarm signals. Curr. Biol. 30, 2761\u20132776.e7 (2020).","journal-title":"Curr. Biol."},{"key":"2442_CR56","doi-asserted-by":"publisher","first-page":"554","DOI":"10.4049\/jimmunol.2000265","volume":"206","author":"Z Xu","year":"2021","unstructured":"Xu, Z., Lin, C. C., Ho, S., Vlad, G. & Suciu-Foca, N. Suppression of experimental autoimmune encephalomyelitis by ILT3.Fc. J. Immunol. 206, 554\u2013565 (2021).","journal-title":"J. Immunol."},{"key":"2442_CR57","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.cell.2004.10.010","volume":"119","author":"E Passegue","year":"2004","unstructured":"Passegue, E., Wagner, E. F. & Weissman, I. L. JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells. Cell 119, 431\u2013443 (2004).","journal-title":"Cell"},{"key":"2442_CR58","doi-asserted-by":"crossref","unstructured":"Ogawa, H. et al. Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage. Lupus Sci. Med. 10, e001042 (2023).","DOI":"10.1136\/lupus-2023-001042"},{"key":"2442_CR59","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1186\/s13287-022-03100-x","volume":"13","author":"J Zhang","year":"2022","unstructured":"Zhang, J. et al. Mesenchymal stem cell-derived extracellular vesicles protect retina in a mouse model of retinitis pigmentosa by anti-inflammation through miR-146a-Nr4a3 axis. Stem Cell Res. Ther. 13, 394 (2022).","journal-title":"Stem Cell Res. Ther."},{"key":"2442_CR60","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1161\/CIRCRESAHA.121.320157","volume":"130","author":"L Gan","year":"2022","unstructured":"Gan, L. et al. Ischemic heart-derived small extracellular vesicles impair adipocyte function. Circ. Res. 130, 48\u201366 (2022).","journal-title":"Circ. Res."},{"key":"2442_CR61","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41586-023-06114-4","volume":"618","author":"G Wang","year":"2023","unstructured":"Wang, G. et al. Tumour extracellular vesicles and particles induce liver metabolic dysfunction. Nature 618, 374\u2013382 (2023).","journal-title":"Nature"},{"key":"2442_CR62","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1161\/CIRCULATIONAHA.123.066911","volume":"149","author":"T Caller","year":"2024","unstructured":"Caller, T. et al. Small extracellular vesicles from infarcted and failing heart accelerate tumor growth. Circulation 149, 1729\u20131748 (2024).","journal-title":"Circulation"},{"key":"2442_CR63","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.cell.2019.09.005","volume":"179","author":"MR Puno","year":"2019","unstructured":"Puno, M. R., Weick, E. M., Das, M. & Lima, C. D. SnapShot: the RNA exosome. Cell 179, 282\u2013282.e1 (2019).","journal-title":"Cell"},{"key":"2442_CR64","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.ebiom.2019.06.016","volume":"45","author":"Z Zhang","year":"2019","unstructured":"Zhang, Z. et al. Clearance of apoptotic cells by mesenchymal stem cells contributes to immunosuppression via PGE2. EBioMedicine 45, 341\u2013350 (2019).","journal-title":"EBioMedicine"},{"key":"2442_CR65","first-page":"288","volume":"29","author":"DD Gladman","year":"2002","unstructured":"Gladman, D. D., Ibanez, D. & Urowitz, M. B. Systemic lupus erythematosus disease activity index 2000. J. Rheumatol. 29, 288\u2013291 (2002).","journal-title":"J. Rheumatol."},{"key":"2442_CR66","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.cmet.2023.11.012","volume":"36","author":"Q Ou","year":"2024","unstructured":"Ou, Q. et al. Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation. Cell Metab. 36, 78\u201389.e5 (2024).","journal-title":"Cell Metab."},{"key":"2442_CR67","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/s41592-018-0179-8","volume":"15","author":"K Sikorski","year":"2018","unstructured":"Sikorski, K. et al. A high-throughput pipeline for validation of antibodies. Nat. Methods 15, 909\u2013912 (2018).","journal-title":"Nat. Methods"}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02442-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02442-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02442-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:11:06Z","timestamp":1760375466000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02442-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2442"],"URL":"https:\/\/doi.org\/10.1038\/s41392-025-02442-1","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"assertion":[{"value":"4 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"344"}}