{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:58:04Z","timestamp":1753891084307,"version":"3.41.2"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Previously, we achieved large-scale expansion of bone marrow-derived suppressor cells (MDSCs) derived from cluster of differentiation (CD)34<jats:sup>+<\/jats:sup> cells cultured in human umbilical cord blood (hUCB) and demonstrated their immunomodulatory properties. In the present study, we assessed the therapeutic efficacy of hUCB-MDSCs in atopic dermatitis (AD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Dermatophagoides farinae<\/jats:italic> (Df)-induced NC\/Nga mice (clinical score of 7) were treated with hUCB-MDSCs or a control drug. The mechanisms underlying the therapeutic effects of hUCB-MDSCs were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>hUCB-MDSCs demonstrated immunosuppressive effects in both human and mouse CD4<jats:sup>+<\/jats:sup> T cells. hUCB-MDSCs significantly reduced the clinical severity scores, which were associated with histopathological changes, and reduced inflammatory cell infiltration, epidermal hyperplasia, and fibrosis. Furthermore, hUCB-MDSCs decreased the serum levels of immunoglobulin E, interleukin (IL)-4, IL-5, IL-13, IL-17, thymus- and activation-regulated chemokines, and thymic stromal lymphopoietin. Additionally, they altered the expression of the skin barrier function-related proteins filaggrin, involucrin, loricrin, cytokeratin 10, and cytokeratin 14 and suppressed the activation of Df-restimulated T-cells via cell\u2013cell interactions. hUCB-MDSCs promoted skin recovery and maintained their therapeutic effect even after recurrence. Consequently, hUCB-MDSC administration improved Df-induced AD-like skin lesions and restored skin barrier function. Our findings support the potential of hUCB-MDSCs as a novel treatment strategy for AD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1263646","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:23:14Z","timestamp":1704774194000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Skin repair and immunoregulatory effects of myeloid suppressor cells from human cord blood in atopic dermatitis"],"prefix":"10.3389","volume":"14","author":[{"given":"Chang-Hyun","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Min","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sueon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Ik","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-Hyun","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Hwan","family":"Bang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tai-Gyu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084130","article-title":"Molecular mechanisms of atopic dermatitis pathogenesis","volume":"22","author":"Sroka-Tomaszewska","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"84","DOI":"10.2500\/aap.2019.40.4202","article-title":"Pathophysiology of atopic dermatitis: Clinical implications","volume":"40","author":"Kim","year":"2019","journal-title":"Allergy Asthma Proc"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155664","article-title":"Novel pathogenesis of atopic dermatitis from the view of cytokines in mice and humans","volume":"148","author":"Nakajima","year":"2021","journal-title":"Cytokine"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.07.006","article-title":"Which way do we go? Complex interactions in atopic dermatitis pathogenesis","volume":"141","author":"Patrick","year":"2021","journal-title":"J Invest Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9899.1000110","article-title":"Th2 cytokines and atopic dermatitis","volume":"2","author":"Brandt","year":"2011","journal-title":"J Clin Cell Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.11.034","article-title":"Biologics for treatment of atopic dermatitis: Current status and future prospect","volume":"9","author":"Ratchataswan","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B7","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.anai.2020.08.016","article-title":"New treatments in atopic dermatitis","volume":"126","author":"Puar","year":"2021","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41573-021-00266-6","article-title":"Atopic dermatitis: An expanding therapeutic pipeline for a complex disease","volume":"21","author":"Bieber","year":"2022","journal-title":"Nat Rev Drug Discovery"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nri3175","article-title":"Coordinated regulation of myeloid cells by tumours","volume":"12","author":"Gabrilovich","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2174\/0929867311320110006","article-title":"Myeloid derived suppressor cells and their role in diseases","volume":"20","author":"Kong","year":"2013","journal-title":"Curr Med Chem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10163462","article-title":"Decoding the myeloid-derived suppressor cells in lymphoid Malignancies","volume":"10","author":"Papafragkos","year":"2021","journal-title":"J Clin Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.638841","article-title":"Interaction between MDSC and NK cells in solid and hematological Malignancies: Impact on HSCT","volume":"12","author":"Tumino","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020210","article-title":"The functional crosstalk between myeloid-derived suppressor cells and regulatory T cells within the immunosuppressive tumor microenvironment","volume":"13","author":"Haist","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073512","article-title":"Immunometabolism of myeloid-derived suppressor cells: Implications for Mycobacterium tuberculosis infection and insights from tumor biology","volume":"23","author":"Munansangu","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/sji.12140","article-title":"Passive transfer of tumour-derived MDSCs inhibits asthma-related airway inflammation","volume":"79","author":"Song","year":"2014","journal-title":"Scand J Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1038\/s41598-018-21856-2","article-title":"Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice","volume":"8","author":"Park","year":"2018","journal-title":"Sci Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12742","article-title":"Anti-psoriatic effect of myeloid-derived suppressor cells on imiquimod-induced skin inflammation in mice","volume":"89","author":"Kim","year":"2019","journal-title":"Scand J Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2021.104302","article-title":"Myeloid-derived suppressor cells (MDSC): When good intentions go awry","volume":"362","author":"Sanchez-Pino","year":"2021","journal-title":"Cell Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000176","article-title":"Gamma Delta T cells regulate wound myeloid cell activity after burn","volume":"42","author":"Rani","year":"2014","journal-title":"Shock"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-259549","article-title":"Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells","volume":"117","author":"Mahdipour","year":"2011","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14470","article-title":"Role of nitric oxide in regulating epidermal permeability barrier function","volume":"31","author":"Man","year":"2022","journal-title":"Exp Dermatol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.07.004","article-title":"Ex vivo generated human cord blood myeloid-derived suppressor cells attenuate murine chronic graft-versus-host diseases","volume":"24","author":"Lim","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00183","article-title":"GM-CSF promotes the expansion and differentiation of cord blood myeloid-derived suppressor cells, which attenuate xenogeneic graft-vs.-host disease","volume":"10","author":"Park","year":"2019","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02659.x","article-title":"Therapeutic effects of combination using glucosamine plus tacrolimus (FK-506) on the development of atopic dermatitis-like skin lesions in NC\/Nga mice","volume":"75","author":"Kim","year":"2012","journal-title":"Scand J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1159\/000053599","article-title":"NC\/Nga mice: A mouse model for atopic dermatitis","author":"Suto","year":"1999","journal-title":"Int Arch Allergy Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.18225","article-title":"Atopic dermatitis: Pathomechanisms and lessons learned from novel systemic therapeutic options","volume":"36","author":"Bieber","year":"2022","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.01986.x","article-title":"Mesenchymal progenitor cells in human umbilical cord blood","volume":"109","author":"Erices","year":"2000","journal-title":"Br J Haematol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/cei.12143","article-title":"Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses","volume":"174","author":"Rieber","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15283\/ijsc.2008.1.1.1","article-title":"Mesenchymal stem cell delivery routes and fate","volume":"1","author":"Kurtz","year":"2008","journal-title":"Int J Stem Cells"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.575993","article-title":"Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia","volume":"41","author":"Pendharkar","year":"2010","journal-title":"Stroke"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2217\/rme.13.2","article-title":"Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients","volume":"8","author":"Rosado-de-Castro","year":"2013","journal-title":"Regener Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13287-017-0533-2","article-title":"Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health","volume":"8","author":"Fabian","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.3933","article-title":"Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells","volume":"181","author":"Casiraghi","year":"2008","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.01.026","article-title":"MdSc. MDSC in autoimmunity","volume":"11","author":"Cripps","year":"2011","journal-title":"Int Immunopharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2019.03.001","article-title":"Burn injury is associated with an infiltration of the wound site with myeloid-derived suppressor cells","volume":"338","author":"Schwacha","year":"2019","journal-title":"Cell Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111676","article-title":"Five functional aspects of the epidermal barrier","volume":"22","author":"Lef\u00e8vre-Utile","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2001.03946.x","article-title":"Impairment of skin barrier function in NC\/Nga Tnd mice as a possible model for atopic dermatitis","volume":"144","author":"Aioi","year":"2001","journal-title":"Br J Dermatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57416","article-title":"Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases","volume":"122","author":"Kubo","year":"2012","journal-title":"J Clin Invest"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12495","article-title":"Pathogenesis of atopic dermatitis","volume":"45","author":"Peng","year":"2015","journal-title":"Clin Exp Allergy"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.08.007","article-title":"The role of tight junctions in skin barrier function and dermal absorption","volume":"242","author":"B\u00e4sler","year":"2016","journal-title":"J Control Release"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2017.2985","article-title":"Expression of keratin 1, keratin 10, desmoglein 1 and desmocollin 1 in the epidermis: Possible downregulation by interleukin-4 and interleukin-13 in atopic dermatitis","volume":"27","author":"Totsuka","year":"2017","journal-title":"Eur J Dermatol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147531","article-title":"Cera flava alleviates atopic dermatitis by activating skin barrier function via immune regulation","volume":"22","author":"Park","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/jidsymp.2011.1","article-title":"The role of chronic inflammation in cutaneous fibrosis: Fibroblast growth factor receptor deficiency in keratinocytes as an example","volume":"15","author":"Meyer","year":"2011","journal-title":"J Investig Dermatol Symp Proc"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0503","article-title":"Epidermal differentiation in barrier maintenance and wound healing","volume":"3","author":"Wikramanayake","year":"2014","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-5699(98)01285-7","article-title":"A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis","volume":"19","author":"Grewe","year":"1998","journal-title":"Immunol Today"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1016\/j.jaci.2009.03.041","article-title":"IL-22-producing \u201cT22\u201d T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells","volume":"123","author":"Nograles","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-008-0912-8","article-title":"Contribution of itch-associated scratch behavior to the development of skin lesions in Dermatophagoides farinae-induced dermatitis model in NC\/Nga mice","volume":"301","author":"Yamamoto","year":"2009","journal-title":"Arch Dermatol Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051745","article-title":"Thymic stromal lymphopoietin: Master switch for allergic inflammation","volume":"203","author":"Liu","year":"2006","journal-title":"J Exp Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2004.01.001","article-title":"Both Th2 and Th1 chemokines (TARC\/CCL17, MDC\/CCL22, and Mig\/CXCL9) are elevated in sera from patients with atopic dermatitis","volume":"34","author":"Shimada","year":"2004","journal-title":"J Dermatol Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/nu12010249","article-title":"Fermented Morinda citrifolia (Noni) alleviates DNCB-induced atopic dermatitis in NC\/Nga mice through modulating immune balance and skin barrier function","volume":"12","author":"Kim","year":"2020","journal-title":"Nutrients"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.134","article-title":"The influence of TSLP on the allergic response","volume":"3","author":"Comeau","year":"2010","journal-title":"Mucosal Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.104793","article-title":"Clinical improvement and immunohistochemical findings in severe atopic dermatitis treated with interferon gamma","volume":"42","author":"Jang","year":"2000","journal-title":"J Am Acad Dermatol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2016.1135898","article-title":"Recent considerations in the use of recombinant interferon gamma for biological therapy of atopic dermatitis","volume":"16","author":"Brar","year":"2016","journal-title":"Expert Opin Biol Ther"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010089","article-title":"The dark side of IFN-\u03b3: Its role in promoting cancer immunoevasion","volume":"19","author":"Mojic","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-019-01237-9","article-title":"Adoptive transfer of IFN-\u03b3-induced M-MDSCs promotes immune tolerance to allografts through iNOS pathway","volume":"68","author":"Yang","year":"2019","journal-title":"Inflammation Res"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.723544","article-title":"GVHD pathogenesis, prevention and treatment: Lessons from humanized mouse transplant models","volume":"12","author":"Hess","year":"2021","journal-title":"Front Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.30365","article-title":"Recent advance in mesenchymal stem cells therapy for atopic dermatitis","volume":"124","author":"Najera","year":"2023","journal-title":"J Cell Biochem"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1263646\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:23:18Z","timestamp":1704774198000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1263646\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,9]]},"references-count":58,"alternative-id":["10.3389\/fimmu.2023.1263646"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1263646","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2024,1,9]]},"article-number":"1263646"}}