Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation
Abstract Rheumatoid arthritis (RA) is an autoimmune disease that causes joint swelling and inflammation and can involve the entire body. RA is characterized by the increase of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor, and the over-activation of T lymphocytes and...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01054-y |
| _version_ | 1797831935595118592 |
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| author | JooYeon Jhun Jeonghyeon Moon Ji Ye Kwon Keun-Hyung Cho Seang Yoon Lee Hyun Sik Na Mi-La Cho Jun-Ki Min |
| author_facet | JooYeon Jhun Jeonghyeon Moon Ji Ye Kwon Keun-Hyung Cho Seang Yoon Lee Hyun Sik Na Mi-La Cho Jun-Ki Min |
| author_sort | JooYeon Jhun |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) is an autoimmune disease that causes joint swelling and inflammation and can involve the entire body. RA is characterized by the increase of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor, and the over-activation of T lymphocytes and B lymphocytes, which may lead to severe chronic inflammation of joints. However, despite numerous studies the pathogenesis and treatment of RA remain unresolved. This study investigated the use of small heterodimer partner-interacting leucine zipper protein (SMILE) overexpression to treat a mouse model of RA. SMILE is an insulin-inducible corepressor through adenosine monophosphate-activated kinase (AMPK) signaling pathway. The injection of a SMILE overexpression vector to mice with collagen induced-arthritis resulted in a milder clinical pathology and a reduced incidence of arthritis, less joint tissue damage, and lower levels of Th17 cells and plasma B cells in the spleen. Immunohistochemistry of the joint tissue showed that SMILE decreased B-cell activating factor (BAFF) receptor (BAFF-R), mTOR, and STAT3 expression but increased AMPK expression. In SMILE-overexpressing transgenic mice with collagen antibody-induced arthritis (CAIA), a decrease in the arthritis score and reductions in tissue damage, the number of B cells, and antibody production were observed. The treatment of immune cells in vitro with curcumin, a known SMILE-inducing agent, led to decreases in plasma B cells, germinal center B cells, IL-17-producing B cells, and BAFF-R-positive B cells. Taken together, our findings demonstrate the therapeutic potential of SMILE in RA, based on its inhibition of B cell activation mediated by the AMPK/mTOR and STAT3 signaling pathway and BAFF-R expression. Video abstract |
| first_indexed | 2024-04-09T14:00:47Z |
| format | Article |
| id | doaj.art-173ad8f7b5f74ca58e9e284765cac4db |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-09T14:00:47Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-173ad8f7b5f74ca58e9e284765cac4db2023-05-07T11:18:47ZengBMCCell Communication and Signaling1478-811X2023-05-0121111410.1186/s12964-023-01054-ySmall heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activationJooYeon Jhun0Jeonghyeon Moon1Ji Ye Kwon2Keun-Hyung Cho3Seang Yoon Lee4Hyun Sik Na5Mi-La Cho6Jun-Ki Min7Rheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaDepartments of Neurology and Immunobiology, Yale School of MedicineRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaRheumatism Research Center, College of Medicine, Catholic Research Institute of Medical Science, The Catholic University of KoreaDepartment of Internal Medicine, The Clinical Medicine Research Institute of Bucheon St. Mary’s HospitalAbstract Rheumatoid arthritis (RA) is an autoimmune disease that causes joint swelling and inflammation and can involve the entire body. RA is characterized by the increase of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor, and the over-activation of T lymphocytes and B lymphocytes, which may lead to severe chronic inflammation of joints. However, despite numerous studies the pathogenesis and treatment of RA remain unresolved. This study investigated the use of small heterodimer partner-interacting leucine zipper protein (SMILE) overexpression to treat a mouse model of RA. SMILE is an insulin-inducible corepressor through adenosine monophosphate-activated kinase (AMPK) signaling pathway. The injection of a SMILE overexpression vector to mice with collagen induced-arthritis resulted in a milder clinical pathology and a reduced incidence of arthritis, less joint tissue damage, and lower levels of Th17 cells and plasma B cells in the spleen. Immunohistochemistry of the joint tissue showed that SMILE decreased B-cell activating factor (BAFF) receptor (BAFF-R), mTOR, and STAT3 expression but increased AMPK expression. In SMILE-overexpressing transgenic mice with collagen antibody-induced arthritis (CAIA), a decrease in the arthritis score and reductions in tissue damage, the number of B cells, and antibody production were observed. The treatment of immune cells in vitro with curcumin, a known SMILE-inducing agent, led to decreases in plasma B cells, germinal center B cells, IL-17-producing B cells, and BAFF-R-positive B cells. Taken together, our findings demonstrate the therapeutic potential of SMILE in RA, based on its inhibition of B cell activation mediated by the AMPK/mTOR and STAT3 signaling pathway and BAFF-R expression. Video abstracthttps://doi.org/10.1186/s12964-023-01054-ySmall heterodimer partner-interacting leucine zipper protein (SMILE)Rheumatoid arthritis (RA)B cellBAFF receptorAMPK/mTOR |
| spellingShingle | JooYeon Jhun Jeonghyeon Moon Ji Ye Kwon Keun-Hyung Cho Seang Yoon Lee Hyun Sik Na Mi-La Cho Jun-Ki Min Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation Cell Communication and Signaling Small heterodimer partner-interacting leucine zipper protein (SMILE) Rheumatoid arthritis (RA) B cell BAFF receptor AMPK/mTOR |
| title | Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation |
| title_full | Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation |
| title_fullStr | Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation |
| title_full_unstemmed | Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation |
| title_short | Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation |
| title_sort | small heterodimer partner interacting leucine zipper protein smile ameliorates autoimmune arthritis via ampk signaling pathway and the regulation of b cell activation |
| topic | Small heterodimer partner-interacting leucine zipper protein (SMILE) Rheumatoid arthritis (RA) B cell BAFF receptor AMPK/mTOR |
| url | https://doi.org/10.1186/s12964-023-01054-y |
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