期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms222312988
关键词
breg cells; IL-35; type 1 diabetes
资金
- Swedish Research Council
- Swedish Diabetes Foundation
- Novo Nordisk Foundation
- Barndiabetesfonden
- O.E. och Edla Johanssons
- Sederholm
- Magnus Bergvalls Stiftelse
- Ernfors Fund SEB-Diabetesfonden
- Olga Joensson
- EFIS-IL fellowship
Research has shown that the proportions of Breg cells and IL-35(+) Breg cells are lower in T1D patients. However, treatment with IL-35 can increase the proportions of Breg cells and IL-35(+) Breg cells, preventing the occurrence of hyperglycemia.
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-gamma(+) 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-gamma(+) 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.
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