Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells

• Published in: International journal of molecular sciences Vol. 22; no. 23; p. 12988
• Main Authors: Luo, Zhengkang, Lundin, Sara, Mejia-Cordova, Mariela, Hassani, Imane, Blixt, Martin, Hjelmqvist, Daisy, Lau, Joey, Espes, Daniel, Carlsson, Per-Ola, Sandler, Stellan, Singh, Kailash
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.11.2021; MDPI
• Subjects: Adult; Animals; Anti-Inflammatory Agents - blood; Anti-Inflammatory Agents - pharmacology; Autoimmune diseases; B-Lymphocytes, Regulatory - immunology; breg cells; Cells, Cultured; Cytokines; Diabetes; Diabetes Mellitus, Type 1 - prevention & control; Disease; Disease Models, Animal; Female; Genotype & phenotype; Humans; Hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - prevention & control; IL-35; Immune system; Interferon-gamma - blood; Interleukins - blood; Interleukins - pharmacology; Lymphocyte Count; Male; Mice; Mice, Inbred NOD; Streptozocin - toxicity; type 1 diabetes; type 1 diabetes; IL-35; breg cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222312988

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+ 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+ 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+ 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+ Breg cells. A higher proportion of IFN-γ+ 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+ 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.