Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 배상철 | - |
dc.date.accessioned | 2022-08-02T04:17:15Z | - |
dc.date.available | 2022-08-02T04:17:15Z | - |
dc.date.issued | 2020-10 | - |
dc.identifier.citation | THERANOSTICS, v. 10, no. 22, page. 10186-10199 | en_US |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://www.thno.org/v10p10186.htm | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/171984 | - |
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. | en_US |
dc.description.sponsorship | This study was supported by grants funded by the National Research Foundation of Korea (2017R1A5A2015541, 2017M3A9B4050336, and 2020R1A2C2004200). | en_US |
dc.language.iso | en | en_US |
dc.publisher | IVYSPRING INT PUBL | en_US |
dc.subject | B cell | en_US |
dc.subject | CXCL10 | en_US |
dc.subject | mesenchymal stem cell | en_US |
dc.subject | PD-L1 | en_US |
dc.subject | phorbol ester | en_US |
dc.subject | systemic lupus erythematosus | en_US |
dc.title | Phorbol ester activates human mesenchymal stem cells to inhibit B cells and ameliorate lupus symptoms in MRL.Fas(lpr) mice | en_US |
dc.type | Article | en_US |
dc.relation.no | 22 | - |
dc.relation.volume | 10 | - |
dc.identifier.doi | 10.7150/thno.46835 | - |
dc.relation.page | 10186-10199 | - |
dc.relation.journal | THERANOSTICS | - |
dc.contributor.googleauthor | Lee, Hong Kyung | - |
dc.contributor.googleauthor | Kim, Hyung Sook | - |
dc.contributor.googleauthor | Pyo, Minji | - |
dc.contributor.googleauthor | Park, Eun Jae | - |
dc.contributor.googleauthor | Jang, Sundong | - |
dc.contributor.googleauthor | Jun, Hye Won | - |
dc.contributor.googleauthor | Lee, Tae Yong | - |
dc.contributor.googleauthor | Kim, Kyung Suk | - |
dc.contributor.googleauthor | Bae, Sang-Cheol | - |
dc.contributor.googleauthor | Kim, Youngsoo | - |
dc.relation.code | 2020045642 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | scbae | - |
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