{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:44:45Z","timestamp":1793814285803,"version":"4.6.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores. Quantitative real-time PCR (Q-PCR), western blot and flow cytometry were performed to evaluate the immunomodulatory effects of hUC-MSC-sEVs on macrophages and T regulatory cells (Tregs) both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, and the <jats:italic>in vitro<\/jats:italic> T cell proliferation was detected by Bromodeoxyuridine (BrdU) assay. In addition, high expression of miR-100-5p in hUC-MSC-sEVs was identified by Q-PCR, and the functional role of sEVs-miR-100-5p on macrophages was explored by a series of co-culture experiments using sEVs derived from hUC-MSCs transfected with miR-100-5p inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We firstly demonstrated that hUC-MSC-sEVs had the preventive and therapeutical effects on rabbit autoimmune dacryoadenitis, an animal model of Sj\u00f6gren\u2019s syndrome (SS) dry eye. Further investigation revealed that hUC-MSC-sEVs administration effectively elicited macrophages into an anti-inflammatory M2 phenotype and elevated the proportion of Tregs both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, which contributed to reduced inflammation and improved tissue damage. Importantly, hUC-MSC-sEVs-educated macrophages with M2-like phenotype exhibited strong capacity to inhibit CD4+ T cell proliferation and promote Treg generation <jats:italic>in vitro<\/jats:italic>. Mechanistically, miR-100-5p was highly enriched in hUC-MSC-sEVs, and knockdown of miR-100-5p in hUC-MSC-sEVs partially blunted the promotion of hUC-MSC-sEVs on M2 macrophage polarization and even attenuated the effect of hUC-MSC-sEVs-educated macrophages on T cell suppression and Treg expansion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicated that hUC-MSC-sEVs alleviated autoimmune dacryoadenitis by promoting M2 macrophage polarization and Treg generation possibly through shuttling miR-100-5p. This study sheds new light on the application of MSC-sEVs as a promising therapeutic method for SS dry eye.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.888949","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T16:45:47Z","timestamp":1657125947000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":53,"title":["MSC-Derived Small Extracellular Vesicles Attenuate Autoimmune Dacryoadenitis by Promoting M2 Macrophage Polarization and Inducing Tregs via miR-100-5p"],"prefix":"10.3389","volume":"13","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Nian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000001865","article-title":"Sjogren's Syndrome: More Than Just Dry Eye","volume":"38","author":"Akpek","year":"2019","journal-title":"Cornea"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.09.003","article-title":"A Link Between Interferon and Augmented Plasmin Generation in Exocrine Gland Damage in Sjogren's Syndrome","volume":"40","author":"Gliozzi","year":"2013","journal-title":"J Autoimmun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2174\/1381612821666150316120024","article-title":"Mouse Models of Primary Sjogren's Syndrome","volume":"21","author":"Park","year":"2015","journal-title":"Curr Pharm Des"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1586\/1744666x.2014.900441","article-title":"Macrophages: Important Players in Primary Sjogren's Syndrome","volume":"10","author":"Zhou","year":"2014","journal-title":"Expert Rev Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.05.014","article-title":"Critical Involvement of Macrophage Infiltration in the Development of Sjogren's Syndrome-Associated Dry Eye","volume":"181","author":"Zhou","year":"2012","journal-title":"Am J Pathol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107905","article-title":"Human Umbilical Cord Mesenchymal Stem Cells Alleviate Ongoing Autoimmune Dacryoadenitis in Rabbits via Polarizing Macrophages Into an Anti-Inflammatory Phenotype","volume":"191","author":"Lu","year":"2019","journal-title":"Exp eye Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12910","article-title":"Implications of Macrophage Polarization in Autoimmunity","volume":"154","author":"Funes","year":"2018","journal-title":"Immunology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44490","article-title":"An Unrestrained Proinflammatory M1 Macrophage Population Induced by Iron Impairs Wound Healing in Humans and Mice","volume":"121","author":"Sindrilaru","year":"2011","journal-title":"J Clin Invest"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjophth-2017-000078","article-title":"Kinetics of Corneal Antigen Presenting Cells in Experimental Dry Eye Disease","volume":"1","author":"Lee","year":"2017","journal-title":"BMJ Open Ophthalmol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s00005-015-0335-0","article-title":"Macrophage Phenotype in the Ocular Surface of Experimental Murine Dry Eye Disease","volume":"63","author":"You","year":"2015","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429","article-title":"Macrophage Plasticity, Polarization, and Function in Health and Disease","volume":"233","author":"Shapouri-Moghaddam","year":"2018","journal-title":"J Cell Physiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12756","article-title":"Inverse Correlation Between the Number of CXCR3(+) Macrophages and the Severity of Inflammatory Lesions in Sjogren's Syndrome Salivary Glands: A Pilot Study","volume":"47","author":"Aota","year":"2018","journal-title":"J Oral Pathol Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.102369","article-title":"Macrophages With Regulatory Functions, a Possible New Therapeutic Perspective in Autoimmune Diseases","volume":"18","author":"Di Benedetto","year":"2019","journal-title":"Autoimmun Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12439","article-title":"Reversible Lacrimal Gland-Protective Regulatory T-Cell Dysfunction Underlies Male-Specific Autoimmune Dacryoadenitis in the Non-Obese Diabetic Mouse Model of Sjogren Syndrome","volume":"145","author":"Lieberman","year":"2015","journal-title":"Immunology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12948","article-title":"Salivary-Gland-Protective Regulatory T-Cell Dysfunction Underlies Female-Specific Sialadenitis in the Non-Obese Diabetic Mouse Model of Sjogren Syndrome","volume":"155","author":"Barr","year":"2018","journal-title":"Immunology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7150\/thno.21072","article-title":"Mesenchymal Stem Cells-Derived Exosomes Are More Immunosuppressive Than Microparticles in Inflammatory Arthritis","volume":"8","author":"Cosenza","year":"2018","journal-title":"Theranostics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40364-019-0159-x","article-title":"Exosomes From Mesenchymal Stem\/Stromal Cells: A New Therapeutic Paradigm","volume":"7","author":"Yin","year":"2019","journal-title":"Biomark Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01912","article-title":"Immunomodulatory Effects of Mesenchymal Stem Cells and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Rheumatoid Arthritis","volume":"11","author":"Liu","year":"2020","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121605","article-title":"Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases","volume":"8","author":"Harrell","year":"2019","journal-title":"Cells"},{"key":"B20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13578-020-00427-x","article-title":"Extracellular Vesicles Derived From Different Sources of Mesenchymal Stem Cells: Therapeutic Effects and Translational Potential","volume":"10","author":"Cai","year":"2020","journal-title":"Cell Biosci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-020-10040-7","article-title":"Immunosuppressive Effects of Mesenchymal Stem Cells-Derived Exosomes","volume":"17","author":"Qian","year":"2020","journal-title":"Stem Cell Rev Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2564","article-title":"Exosomal miR-146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin-1beta-Primed Mesenchymal Stem Cells Against Sepsis","volume":"35","author":"Song","year":"2017","journal-title":"Stem Cells"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.2843","article-title":"Isolation and Characterization of Mesenchymal Stem Cells From Whole Human Umbilical Cord Applying a Single Enzyme Approach","volume":"30","author":"Zhang","year":"2012","journal-title":"Cell Biochem Funct"},{"key":"B24","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13287-020-02068-w","article-title":"microRNA-27b Shuttled by Mesenchymal Stem Cell-Derived Exosomes Prevents Sepsis by Targeting JMJD3 and Downregulating NF-kappaB Signaling Pathway","volume":"12","author":"Sun","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"B25","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1097\/ICO.0b013e31823f8e47","article-title":"Autoimmune Dacryoadenitis and Sialadenitis Induced in Rabbits by Intravenous Injection of Autologous Lymphocytes Activated Ex Vivo Against Lacrimal Antigens","volume":"31","author":"Wei","year":"2012","journal-title":"Cornea"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17824","article-title":"Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a Rabbit Model of Induced Autoimmune Dacryoadenitis","volume":"57","author":"Li","year":"2016","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01149","article-title":"Investigation of Circulating Extracellular Vesicle MicroRNA Following Two Consecutive Bouts of Muscle-Damaging Exercise","volume":"9","author":"Lovett","year":"2018","journal-title":"Front Physiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.3390\/pharmaceutics13091439","article-title":"The Protective Effect of Topical Spermidine on Dry Eye Disease With Retinal Damage Induced by Diesel Particulate Matter2","volume":"13","author":"Lee","year":"2021","journal-title":"5 Pharmaceutics"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/jci59643","article-title":"Macrophage Plasticity and Polarization: In Vivo Veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","first-page":"15559","DOI":"10.1038\/s41598-019-52085-w","article-title":"Chloroquine Modulates Inflammatory Autoimmune Responses Through Nurr1 in Autoimmune Diseases","volume":"9","author":"Park","year":"2019","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2018.02.372","article-title":"Mesenchymal Stromal Cell Exosome-Enhanced Regulatory T-Cell Production Through an Antigen-Presenting Cell-Mediated Pathway","volume":"20","author":"Zhang","year":"2018","journal-title":"Cytotherapy"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.12.021","article-title":"Mesenchymal Stem Cell Exosomes Promote Immunosuppression of Regulatory T Cells in Asthma","volume":"363","author":"Du","year":"2018","journal-title":"Exp Cell Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.34","article-title":"Human Macrophages Induce CD4(+)Foxp3(+) Regulatory T Cells via Binding and Re-Release of TGF-Beta","volume":"94","author":"Schmidt","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s12964-020-00650-6","article-title":"Exosomal microRNAs Derived From Mesenchymal Stem Cells: Cell-to-Cell Messages","volume":"18","author":"Asgarpour","year":"2020","journal-title":"Cell Communication Signaling CCS"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nature23282","article-title":"Hypothalamic Stem Cells Control Ageing Speed Partly Through Exosomal miRNAs","volume":"548","author":"Zhang","year":"2017","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0367","article-title":"Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-\u03b2\/SMAD2 Pathway During Wound Healing","volume":"5","author":"Fang","year":"2016","journal-title":"Stem Cells Trans Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey344","article-title":"Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Accelerate Growth of VK2 Vaginal Epithelial Cells Through MicroRNAs In Vitro","volume":"34","author":"Zhu","year":"2019","journal-title":"Hum Reprod"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3204","article-title":"Exosomal miRNA-17-5p Derived From Human Umbilical Cord Mesenchymal Stem Cells Improves Ovarian Function in Premature Ovarian Insufficiency by Regulating SIRT7","volume":"38","author":"Ding","year":"2020","journal-title":"Stem Cells"},{"key":"B39","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41389-018-0106-y","article-title":"miR-100 Maintains Phenotype of Tumor-Associated Macrophages by Targeting mTOR to Promote Tumor Metastasis via Stat5a\/IL-1ra Pathway in Mouse Breast Cancer","volume":"7","author":"Wang","year":"2018","journal-title":"Oncogenesis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics10120999","article-title":"Clinical Applications of Mesenchymal Stem\/Stromal Cell Derived Extracellular Vesicles: Therapeutic Potential of an Acellular Product","volume":"10","author":"Massa","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.1038\/s41598-017-04559-y","article-title":"Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis","volume":"7","author":"Bai","year":"2017","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2092315","article-title":"Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjogren's Syndrome","volume":"2018","author":"Hai","year":"2018","journal-title":"Stem Cells Int"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.04.020","article-title":"Comprehensive Molecular Profiles of Functionally Effective MSC-Derived Extracellular Vesicles in Immunomodulation","volume":"28","author":"Kim","year":"2020","journal-title":"Mol Ther"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02594","article-title":"CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjogren's Syndrome","volume":"9","author":"Ushio","year":"2018","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1186\/s13287-020-01937-8","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Alter Disease Outcomes via Endorsement of Macrophage Polarization","volume":"11","author":"Wang","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.16-0363","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization","volume":"6","author":"Lo Sicco","year":"2017","journal-title":"Stem Cells Trans Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45444","article-title":"Kruppel-Like Factor 4 Regulates Macrophage Polarization","volume":"121","author":"Liao","year":"2011","journal-title":"J Clin Invest"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU1018-378RR","article-title":"M2b Macrophage Polarization and Its Roles in Diseases","volume":"106","author":"Wang","year":"2019","journal-title":"J Leukoc Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490","article-title":"Control of Regulatory T Cell Development by the Transcription Factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"474","DOI":"10.3390\/pharmaceutics12050474","article-title":"Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: From Basic Science to Clinics","volume":"12","author":"Harrell","year":"2020","journal-title":"Pharmaceutics"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27260","article-title":"Immunomodulatory Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Type-1 Autoimmune Diabetes","volume":"119","author":"Nojehdehi","year":"2018","journal-title":"J Cell Biochem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-016-0803-z","article-title":"Transcriptional Modulation of Regulatory T Cell Development by Novel Regulators NR4As","volume":"39","author":"Won","year":"2016","journal-title":"Arch Pharm Res"},{"key":"B53","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/ncomms1272","article-title":"The Nuclear Orphan Receptor Nr4a2 Induces Foxp3 and Regulates Differentiation of CD4+ T Cells","volume":"2","author":"Sekiya","year":"2011","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.329","article-title":"A Positive-Feedback Loop Between Tumour Infiltrating Activated Treg Cells and Type 2-Skewed Macrophages Is Essential for Progression of Laryngeal Squamous Cell Carcinoma","volume":"117","author":"Sun","year":"2017","journal-title":"Br J Cancer"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00680","article-title":"The Pivotal Role of Regulatory T Cells in the Regulation of Innate Immune Cells","volume":"10","author":"Okeke","year":"2019","journal-title":"Front Immunol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1186\/s13287-018-1069-9","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Affect Disease Outcomes via Transfer of microRNAs","volume":"9","author":"Qiu","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1723260","article-title":"Small Extracellular Vesicles Derived From Human Mesenchymal Stromal Cells Prevent Group 2 Innate Lymphoid Cell-Dominant Allergic Airway Inflammation Through Delivery of miR-146a-5p","volume":"9","author":"Fang","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"B58","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/s41419-020-02788-0","article-title":"IFN-\u03b3 Promoted Exosomes From Mesenchymal Stem Cells to Attenuate Colitis via miR-125a and miR-125b","volume":"11","author":"Yang","year":"2020","journal-title":"Cell Death Dis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311428","article-title":"MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy","volume":"122","author":"Pankratz","year":"2018","journal-title":"Circ Res"},{"key":"B60","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/imm.12342","article-title":"MicroRNA-100-5p Indirectly Modulates the Expression of Il6, Ptgs1\/2 and Tlr4 mRNA in the Mouse Follicular Dendritic Cell-Like Cell Line, FL-Y","volume":"144","author":"Aungier","year":"2015","journal-title":"Immunology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201910_19265","article-title":"MiR-100 Suppresses Inflammatory Activation of Microglia and Neuronal Apoptosis Following Spinal Cord Injury via TLR4\/NF-\u03bab Pathway","volume":"23","author":"Li","year":"2019","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s13287-020-01610-0","article-title":"Mesenchymal Stem Cell-Derived Exosomes Protect Beta Cells Against Hypoxia-Induced Apoptosis via miR-21 by Alleviating ER Stress and Inhibiting P38 MAPK Phosphorylation","volume":"11","author":"Chen","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B63","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.biomaterials.2019.03.022","article-title":"miR-100-5p-Abundant Exosomes Derived From Infrapatellar Fat Pad MSCs Protect Articular Cartilage and Ameliorate Gait Abnormalities via Inhibition of mTOR in Osteoarthritis","volume":"206","author":"Wu","year":"2019","journal-title":"Biomaterials"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.615850","article-title":"Exosomes of Human Umbilical Cord MSCs Protect Against Hypoxia\/Reoxygenation-Induced Pyroptosis of Cardiomyocytes via the miRNA-100-5p\/FOXO3\/NLRP3 Pathway","volume":"8","author":"Liang","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2018-000701","article-title":"Increased Mtorc1 Activation in Salivary Gland B Cells and T Cells From Patients With Sjogren's Syndrome: mTOR Inhibition as a Novel Therapeutic Strategy to Halt Immunopathology","volume":"5","author":"Blokland","year":"2019","journal-title":"RMD Open"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.888949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T16:45:56Z","timestamp":1657125956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.888949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":65,"alternative-id":["10.3389\/fimmu.2022.888949"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.888949","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]},"article-number":"888949"}}