Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy
Abstract More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01588-9 |
| _version_ | 1797219683018997760 |
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| author | Long He Zhuotai Zhong Shuting Wen Peiwu Li Qilong Jiang Fengbin Liu |
| author_facet | Long He Zhuotai Zhong Shuting Wen Peiwu Li Qilong Jiang Fengbin Liu |
| author_sort | Long He |
| collection | DOAJ |
| description | Abstract More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs. |
| first_indexed | 2024-04-24T12:37:32Z |
| format | Article |
| id | doaj.art-a21b219506104429b8b717a56281817c |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-24T12:37:32Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-a21b219506104429b8b717a56281817c2024-04-07T11:25:24ZengBMCCell Communication and Signaling1478-811X2024-04-0122111610.1186/s12964-024-01588-9Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagyLong He0Zhuotai Zhong1Shuting Wen2Peiwu Li3Qilong Jiang4Fengbin Liu5Department of Digestive Endoscopy, The First Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical SciencesDepartment of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Hepatobiliary, The First Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Myopathies, The First Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Hepatobiliary, The First Affiliated Hospital of Guangzhou University of Chinese MedicineAbstract More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.https://doi.org/10.1186/s12964-024-01588-9Myasthenia gravisTregGut microbiotaButyrateAutophagy |
| spellingShingle | Long He Zhuotai Zhong Shuting Wen Peiwu Li Qilong Jiang Fengbin Liu Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy Cell Communication and Signaling Myasthenia gravis Treg Gut microbiota Butyrate Autophagy |
| title | Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy |
| title_full | Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy |
| title_fullStr | Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy |
| title_full_unstemmed | Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy |
| title_short | Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy |
| title_sort | gut microbiota derived butyrate restores impaired regulatory t cells in patients with achr myasthenia gravis via mtor mediated autophagy |
| topic | Myasthenia gravis Treg Gut microbiota Butyrate Autophagy |
| url | https://doi.org/10.1186/s12964-024-01588-9 |
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