Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells
The anti-inflammatory role of regulatory B cells (Breg cells) has been associated with IL-35 based on studies of experimental autoimmune uveitis and encephalitis. The role of Breg cells and IL-35<sup>+</sup> Breg cells for type 1 diabetes (T1D) remains to be investigated. We studied PBMC...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12988 |
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| author | Zhengkang Luo Sara Lundin Mariela Mejia-Cordova Imane Hassani Martin Blixt Daisy Hjelmqvist Joey Lau Daniel Espes Per-Ola Carlsson Stellan Sandler Kailash Singh |
| author_facet | Zhengkang Luo Sara Lundin Mariela Mejia-Cordova Imane Hassani Martin Blixt Daisy Hjelmqvist Joey Lau Daniel Espes Per-Ola Carlsson Stellan Sandler Kailash Singh |
| author_sort | Zhengkang Luo |
| collection | DOAJ |
| description | The anti-inflammatory role of regulatory B cells (Breg cells) has been associated with IL-35 based on studies of experimental autoimmune uveitis and encephalitis. The role of Breg cells and IL-35<sup>+</sup> Breg cells for type 1 diabetes (T1D) remains to be investigated. We studied PBMCs from T1D subjects and healthy controls (HC) and found lowered proportions of Breg cells and IL-35<sup>+</sup> Breg cells in T1D. To elucidate the role of Breg cells, the lymphoid organs of two mouse models of T1D were examined. Lower proportions of Breg cells and IL-35<sup>+</sup> Breg cells were found in the animal models of T1D compared with control mice. In addition, the systemic administration of recombinant mouse IL-35 prevented hyperglycemia after multiple low dose streptozotocin (MLDSTZ) injections and increased the proportions of Breg cells and IL-35<sup>+</sup> Breg cells. A higher proportion of IFN-γ<sup>+</sup> cells among Breg cells were found in the PBMCs of the T1D subjects. In the MLDSTZ mice, IL-35 administration decreased the proportions of IFN-γ<sup>+</sup> cells among the Breg cells. Our data illustrate that Breg cells may play an important role in the development of T1D and that IL-35 treatment prevents the development of hyperglycemia by maintaining the phenotype of the Breg cells under an experimental T1D condition. |
| first_indexed | 2024-03-10T04:52:12Z |
| format | Article |
| id | doaj.art-54e51940bdee4665960904dd5d9ea963 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:12Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-54e51940bdee4665960904dd5d9ea9632023-11-23T02:31:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231298810.3390/ijms222312988Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B CellsZhengkang Luo0Sara Lundin1Mariela Mejia-Cordova2Imane Hassani3Martin Blixt4Daisy Hjelmqvist5Joey Lau6Daniel Espes7Per-Ola Carlsson8Stellan Sandler9Kailash Singh10Department of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenScience for Life Laboratory, Department of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenThe anti-inflammatory role of regulatory B cells (Breg cells) has been associated with IL-35 based on studies of experimental autoimmune uveitis and encephalitis. The role of Breg cells and IL-35<sup>+</sup> Breg cells for type 1 diabetes (T1D) remains to be investigated. We studied PBMCs from T1D subjects and healthy controls (HC) and found lowered proportions of Breg cells and IL-35<sup>+</sup> Breg cells in T1D. To elucidate the role of Breg cells, the lymphoid organs of two mouse models of T1D were examined. Lower proportions of Breg cells and IL-35<sup>+</sup> Breg cells were found in the animal models of T1D compared with control mice. In addition, the systemic administration of recombinant mouse IL-35 prevented hyperglycemia after multiple low dose streptozotocin (MLDSTZ) injections and increased the proportions of Breg cells and IL-35<sup>+</sup> Breg cells. A higher proportion of IFN-γ<sup>+</sup> cells among Breg cells were found in the PBMCs of the T1D subjects. In the MLDSTZ mice, IL-35 administration decreased the proportions of IFN-γ<sup>+</sup> cells among the Breg cells. Our data illustrate that Breg cells may play an important role in the development of T1D and that IL-35 treatment prevents the development of hyperglycemia by maintaining the phenotype of the Breg cells under an experimental T1D condition.https://www.mdpi.com/1422-0067/22/23/12988breg cellsIL-35type 1 diabetes |
| spellingShingle | Zhengkang Luo Sara Lundin Mariela Mejia-Cordova Imane Hassani Martin Blixt Daisy Hjelmqvist Joey Lau Daniel Espes Per-Ola Carlsson Stellan Sandler Kailash Singh Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells International Journal of Molecular Sciences breg cells IL-35 type 1 diabetes |
| title | Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells |
| title_full | Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells |
| title_fullStr | Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells |
| title_full_unstemmed | Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells |
| title_short | Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells |
| title_sort | interleukin 35 prevents development of autoimmune diabetes possibly by maintaining the phenotype of regulatory b cells |
| topic | breg cells IL-35 type 1 diabetes |
| url | https://www.mdpi.com/1422-0067/22/23/12988 |
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