Phorbol ester activates human mesenchymal stem cells to inhibit B cells and ameliorate lupus symptoms in MRL.Fas(lpr) mice
DC Field | Value | Language |
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dc.contributor.author | Lee, Hong Kyung | - |
dc.contributor.author | Kim, Hyung Sook | - |
dc.contributor.author | Pyo, Minji | - |
dc.contributor.author | Park, Eun Jae | - |
dc.contributor.author | Jang, Sundong | - |
dc.contributor.author | Jun, Hye Won | - |
dc.contributor.author | Lee, Tae Yong | - |
dc.contributor.author | Kim, Kyung Suk | - |
dc.contributor.author | Bae, Sang-Cheol | - |
dc.contributor.author | Kim, Youngsoo | - |
dc.contributor.author | Hong, Jin Tae | - |
dc.contributor.author | Yun, Jaesuk | - |
dc.contributor.author | Han, Sang-Bae | - |
dc.date.accessioned | 2021-08-02T10:27:25Z | - |
dc.date.available | 2021-08-02T10:27:25Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/11543 | - |
dc.description.abstract | Rationale: Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production by hyper-activated B cells. Although mesenchymal stem cells (MSCs) ameliorate lupus symptoms by inhibiting T cells, whether they inhibit B cells has been controversial. Here we address this issue and reveal how to prime MSCs to inhibit B cells and improve the efficacy of MSCs in SLE. Methods: We examined the effect of MSCs on purified B cells in vitro and the therapeutic efficacy of MSCs in lupus-prone MRL.Fas(lpr) mice. We screened chemicals for their ability to activate MSCs to inhibit B cells. Results: Mouse bone marrow-derived MSCs inhibited mouse B cells in a CXCL12-dependent manner, whereas human bone marrow-derived MSCs (hMSCs) did not inhibit human B (hB) cells. We used a chemical approach to overcome this hurdle and found that phorbol myristate acetate (PMA), phorbol 12,13-dibutyrate, and ingenol-3-angelate rendered hMSCs capable of inhibiting IgM production by hB cells. As to the mechanism, PMA-primed hMSCs attracted hB cells in a CXCL10-dependent manner and induced hB cell apoptosis in a PD-L1-dependent manner. Finally, we showed that PMA-primed hMSCs were better than naive hMSCs at ameliorating SLE progression in MRL.Fas(lpr) mice. Conclusion: Taken together, our data demonstrate that phorbol esters might be good tool compounds to activate MSCs to inhibit B cells and suggest that our chemical approach might allow for improvements in the therapeutic efficacy of hMSCs in SLE. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IVYSPRING INT PUBL | - |
dc.title | Phorbol ester activates human mesenchymal stem cells to inhibit B cells and ameliorate lupus symptoms in MRL.Fas(lpr) mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Bae, Sang-Cheol | - |
dc.identifier.doi | 10.7150/thno.46835 | - |
dc.identifier.scopusid | 2-s2.0-85090774671 | - |
dc.identifier.wosid | 000560637200010 | - |
dc.identifier.bibliographicCitation | THERANOSTICS, v.10, no.22, pp.10186 - 10199 | - |
dc.relation.isPartOf | THERANOSTICS | - |
dc.citation.title | THERANOSTICS | - |
dc.citation.volume | 10 | - |
dc.citation.number | 22 | - |
dc.citation.startPage | 10186 | - |
dc.citation.endPage | 10199 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | STROMAL CELLS | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | ANTIBODY-PRODUCTION | - |
dc.subject.keywordPlus | INTERFERON-GAMMA | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | TRANSPLANTATION | - |
dc.subject.keywordPlus | PD-L1 | - |
dc.subject.keywordPlus | ERYTHEMATOSUS | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordAuthor | B cell | - |
dc.subject.keywordAuthor | CXCL10 | - |
dc.subject.keywordAuthor | mesenchymal stem cell | - |
dc.subject.keywordAuthor | PD-L1 | - |
dc.subject.keywordAuthor | phorbol ester | - |
dc.subject.keywordAuthor | systemic lupus erythematosus | - |
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