The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells
Kayoko Kibata,1 Tomoki Ito,1 Muneo Inaba,1 Akihiro Tanaka,1 Ryoichi Iwata,2 Noriko Inagaki-Katashiba,1 Vien Phan,1 Atsushi Satake,1 Shosaku Nomura11Kansai Medical University, First Department of Internal Medicine, Osaka, Japan; 2Kansai Medical University, Department of Neurosurgery, Osaka, JapanBack...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-07-01
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| Series: | Journal of Blood Medicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-immunomodulatory-drug-lenalidomide-sustains-and-enhances-interfero-peer-reviewed-article-JBM |
| _version_ | 1818911082344873984 |
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| author | Kibata K Ito T Inaba M Tanaka A Iwata R Inagaki-Katashiba N Phan V Satake A Nomura S |
| author_facet | Kibata K Ito T Inaba M Tanaka A Iwata R Inagaki-Katashiba N Phan V Satake A Nomura S |
| author_sort | Kibata K |
| collection | DOAJ |
| description | Kayoko Kibata,1 Tomoki Ito,1 Muneo Inaba,1 Akihiro Tanaka,1 Ryoichi Iwata,2 Noriko Inagaki-Katashiba,1 Vien Phan,1 Atsushi Satake,1 Shosaku Nomura11Kansai Medical University, First Department of Internal Medicine, Osaka, Japan; 2Kansai Medical University, Department of Neurosurgery, Osaka, JapanBackground: Lenalidomide (LEN), an immunomodulatory drug (IMiD), is currently used for treatment of multiple myeloma (MM). LEN potentiates T cell and natural killer cell functions. However, the cellular and molecular mechanisms underlying the immunomodulatory effects of LEN remain unclear. We focused on the effects of LEN on human plasmacytoid dendritic cells (pDCs), which are the major source of interferon (IFN)-α in the blood and play a central role in innate immune responses.Results: We found that bortezomib, a proteasome inhibitor used to treat MM, killed pDCs but that 0.1–3 μM LEN (covering clinical plasma concentration range) did not affect pDC survival or CD86 expression. Bortezomib inhibited pDC-derived IFN-α production in a dose-dependent fashion, but 0.1–3 μM LEN sustained pDC-derived IFN-α production when stimulated with an optimal concentration of CpG-ODN 2216 (3 μM). In pDCs stimulated with a low concentration of CpG-ODN (0.1 μM), LEN enhanced IFN-α production. These results indicated that LEN, when used at a clinically relevant concentration, can potentially enhance IFN-α production by pDCs.Conclusion: Collectively, our findings unveiled a novel target of LEN and extend the repertoire of the drug’s known immunomodulatory effects. These effects may explain the low incidence of herpes zoster viral infection observed during LEN treatment compared with bortezomib treatment. LEN may function as an IMiD affecting a wide array of immune cells, including pDCs, leading to amplification of a positive immune axis able to eliminate MM cells.Keywords: lenalidomide, IMiDs, plasmacyotid DCs, type I IFNs, multiple myeloma |
| first_indexed | 2024-12-19T22:53:03Z |
| format | Article |
| id | doaj.art-9e38442f184c4f52bbe271b50060eb0c |
| institution | Directory Open Access Journal |
| issn | 1179-2736 |
| language | English |
| last_indexed | 2024-12-19T22:53:03Z |
| publishDate | 2019-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Blood Medicine |
| spelling | doaj.art-9e38442f184c4f52bbe271b50060eb0c2022-12-21T20:02:43ZengDove Medical PressJournal of Blood Medicine1179-27362019-07-01Volume 1021722647114The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cellsKibata KIto TInaba MTanaka AIwata RInagaki-Katashiba NPhan VSatake ANomura SKayoko Kibata,1 Tomoki Ito,1 Muneo Inaba,1 Akihiro Tanaka,1 Ryoichi Iwata,2 Noriko Inagaki-Katashiba,1 Vien Phan,1 Atsushi Satake,1 Shosaku Nomura11Kansai Medical University, First Department of Internal Medicine, Osaka, Japan; 2Kansai Medical University, Department of Neurosurgery, Osaka, JapanBackground: Lenalidomide (LEN), an immunomodulatory drug (IMiD), is currently used for treatment of multiple myeloma (MM). LEN potentiates T cell and natural killer cell functions. However, the cellular and molecular mechanisms underlying the immunomodulatory effects of LEN remain unclear. We focused on the effects of LEN on human plasmacytoid dendritic cells (pDCs), which are the major source of interferon (IFN)-α in the blood and play a central role in innate immune responses.Results: We found that bortezomib, a proteasome inhibitor used to treat MM, killed pDCs but that 0.1–3 μM LEN (covering clinical plasma concentration range) did not affect pDC survival or CD86 expression. Bortezomib inhibited pDC-derived IFN-α production in a dose-dependent fashion, but 0.1–3 μM LEN sustained pDC-derived IFN-α production when stimulated with an optimal concentration of CpG-ODN 2216 (3 μM). In pDCs stimulated with a low concentration of CpG-ODN (0.1 μM), LEN enhanced IFN-α production. These results indicated that LEN, when used at a clinically relevant concentration, can potentially enhance IFN-α production by pDCs.Conclusion: Collectively, our findings unveiled a novel target of LEN and extend the repertoire of the drug’s known immunomodulatory effects. These effects may explain the low incidence of herpes zoster viral infection observed during LEN treatment compared with bortezomib treatment. LEN may function as an IMiD affecting a wide array of immune cells, including pDCs, leading to amplification of a positive immune axis able to eliminate MM cells.Keywords: lenalidomide, IMiDs, plasmacyotid DCs, type I IFNs, multiple myelomahttps://www.dovepress.com/the-immunomodulatory-drug-lenalidomide-sustains-and-enhances-interfero-peer-reviewed-article-JBMlenalidomideIMiDsplasmacyotid DCstype I IFNsmultiple myeloma |
| spellingShingle | Kibata K Ito T Inaba M Tanaka A Iwata R Inagaki-Katashiba N Phan V Satake A Nomura S The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells Journal of Blood Medicine lenalidomide IMiDs plasmacyotid DCs type I IFNs multiple myeloma |
| title | The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells |
| title_full | The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells |
| title_fullStr | The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells |
| title_full_unstemmed | The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells |
| title_short | The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells |
| title_sort | immunomodulatory drug lenalidomide sustains and enhances interferon alpha production by human plasmacytoid dendritic cells |
| topic | lenalidomide IMiDs plasmacyotid DCs type I IFNs multiple myeloma |
| url | https://www.dovepress.com/the-immunomodulatory-drug-lenalidomide-sustains-and-enhances-interfero-peer-reviewed-article-JBM |
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