{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:38:22Z","timestamp":1788781102135,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute Intramural Research Program"},{"name":"Helena Mishoe Fellowship for Underrepresented Scientists of the NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously reported that granulocytic myeloid-derived suppressor cells (G-MDSCs) suppressed T-cell activation and attenuated bone marrow failure (BMF) in a minor histocompatibility (minor-H) antigen mismatched murine aplastic anemia (AA) model. In the current study, we tested the hypothesis that exosomes, a subset of extracellular vesicles, are responsible at least partially for G-MDSCs\u2019 therapeutic efficacy. Indeed, exosomes isolated from GMDSCs (G-MDSC-exos) suppressed CD4+ and CD8+ T-cell proliferation in vitro and mildly attenuated immune BMF in the minor-H mismatched AA model. G-MDSC-exos treatment significantly increased red blood cells, hemoglobin, and total bone marrow (BM) cells, and moderately reduced BM CD8+ T cells. G-MDSC-exos\u2019 effects were associated with upregulations in an array of lymphocyte-suppression-related miRNAs such as hsa-miR-142-5p, miR-19a-3p, and miR-19b-3p in both BM CD4+ and CD8+ T cells. We concluded that G-MDSC-exos attenuate immune BMF via modulating the delivery of immunosuppressive miRNAs into activated T lymphocytes.<\/jats:p>","DOI":"10.3390\/ijms241914661","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:42:12Z","timestamp":1695865332000},"page":"14661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immunosuppressive Activity of Exosomes from Granulocytic Myeloid-Derived Suppressor Cells in a Murine Model of Immune Bone Marrow Failure"],"prefix":"10.3390","volume":"24","author":[{"given":"Ash Lee","family":"Manley","sequence":"first","affiliation":[{"name":"Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Chen","sequence":"additional","affiliation":[{"name":"Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-8250","authenticated-orcid":false,"given":"Wendy","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Intracellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-2366","authenticated-orcid":false,"given":"Xingmin","family":"Feng","sequence":"additional","affiliation":[{"name":"Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal S.","family":"Young","sequence":"additional","affiliation":[{"name":"Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12964-021-00730-1","article-title":"The exosome journey: From biogenesis to uptake and intracellular signalling","volume":"19","author":"Gurung","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.2147\/IJN.S264498","article-title":"Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications","volume":"15","author":"Zhang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1517\/14712598.2016.1131976","article-title":"Exosomes for repair, regeneration and rejuvenation","volume":"16","author":"Basu","year":"2016","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.4049\/jimmunol.178.7.4159","article-title":"Minor antigen h60-mediated aplastic anemia is ameliorated by immunosuppression and the infusion of regulatory T cells","volume":"178","author":"Chen","year":"2007","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJMra1413485","article-title":"Aplastic Anemia","volume":"379","author":"Young","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11864-017-0511-z","article-title":"Diagnosis and Treatment of Aplastic Anemia","volume":"18","author":"Peslak","year":"2017","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1182\/blood-2016-08-693481","article-title":"How I treat acquired aplastic anemia","volume":"129","author":"Bacigalupo","year":"2017","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.exphem.2004.08.006","article-title":"A mouse model of lymphocyte infusion-induced bone marrow failure","volume":"32","author":"Bloom","year":"2004","journal-title":"Exp. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.3324\/haematol.2018.189449","article-title":"Hematopoietic stem cell loss and hematopoietic failure in severe aplastic anemia is driven by macrophages and aberrant podoplanin expression","volume":"103","author":"McCabe","year":"2018","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/bjh.16871","article-title":"All-trans-retinoic acid shifts Th1 towards Th2 cell differentiation by targeting NFAT1 signalling to ameliorate immune-mediated aplastic anaemia","volume":"191","author":"Tang","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1182\/bloodadvances.2022007254","article-title":"Granulocytic myeloid-derived suppressor cells to prevent and treat murine immune-mediated bone marrow failure","volume":"7","author":"Feng","year":"2023","journal-title":"Blood Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1002\/2211-5463.13504","article-title":"Myoblast-derived exosomes promote the repair and regeneration of injured skeletal muscle in mice","volume":"12","author":"Ji","year":"2022","journal-title":"FEBS Open Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liang, W., Han, B., Hai, Y., Sun, D., and Yin, P. (2021). Mechanism of Action of Mesenchymal Stem Cell-Derived Exosomes in the Intervertebral Disc Degeneration Treatment and Bone Repair and Regeneration. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.833840"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.stemcr.2021.05.003","article-title":"Mesenchymal stromal cell-derived exosomes in cardiac regeneration and repair","volume":"16","author":"Sun","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mancuso, T., Barone, A., Salatino, A., Molinaro, C., Marino, F., Scalise, M., Torella, M., De Angelis, A., Urbanek, K., and Torella, D. (2020). Unravelling the Biology of Adult Cardiac Stem Cell-Derived Exosomes to Foster Endogenous Cardiac Regeneration and Repair. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103725"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhu, D. (2019). G-MDSC-Derived Exosomes Attenuate Collagen-Induced Arthritis by Impairing Th1 and Th17 Cell Responses, Elsevier.","DOI":"10.1016\/j.bbadis.2019.165540"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15356","DOI":"10.18632\/oncotarget.7324","article-title":"Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104276","DOI":"10.1016\/j.cellimm.2020.104276","article-title":"Extracellular vesicles released by myeloid-derived suppressor cells from pregnant women modulate adaptive immune responses","volume":"361","author":"Dietz","year":"2021","journal-title":"Cell Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"588500","DOI":"10.3389\/fimmu.2020.588500","article-title":"Granulocytic Myeloid-Derived Suppressor Cell Exosomal Prostaglandin E2 Ameliorates Collagen-Induced Arthritis by Enhancing IL-10(+) B Cells","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.3324\/haematol.2015.126128","article-title":"Identification of novel microRNA signatures linked to acquired aplastic anemia","volume":"100","author":"Hosokawa","year":"2015","journal-title":"Haematologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1002\/art.34505","article-title":"Decreased microRNA-142-3p\/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus","volume":"64","author":"Ding","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3000605221113918","DOI":"10.1177\/03000605221113918","article-title":"Bioinformatics analysis of mRNA profiles and identification of microRNA-mRNA network in CD4+ T cells in seasonal allergic rhinitis","volume":"50","author":"Jin","year":"2022","journal-title":"J. Int. Med. 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