Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus

El‐Mokhtar, Mohamed A.; Elsherbiny, Nahla M; Sayed, Douaa; Raafat, Duaa Mohamed; Askar, Eman; Hussein, Almontaser; Abdel-Malek, Mohamed A. Y.; Shalaby, Amira M.

doi:10.1155/2020/8935694

Cited by 17 publications

(15 citation statements)

References 38 publications

(46 reference statements)

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“…( 32 ). Previous studies found a decrease of this regulatory B subset in T1D patients ( 33 – 35 ) suggesting that the lower frequencies of transitional B cells found in the present study could be related to an impairment in their regulatory properties. Moreover, here we show that patients at onset of the disease have higher percentages of naïve and IgM-only memory B cells, supporting that B cells can play a role in the pathogenesis of the disease, although more studies focusing on it are lacking.…”

Section: Discussionsupporting

confidence: 58%

Identifying Changes in Peripheral Lymphocyte Subpopulations in Adult Onset Type 1 Diabetes

et al. 2021

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T- and B-lymphocytes play an important role in the pathogenesis of type 1 diabetes (T1D), a chronic disease caused by the autoimmune destruction of the insulin-producing cells in the pancreatic islets. Flow cytometry allows their characterization in peripheral blood, letting to investigate changes in cellular subpopulations that can provide insights in T1D pathophysiology. With this purpose, CD4+ and CD8+ T cells (including naïve, central memory, effector memory and terminally differentiated effector (TEMRA), Th17 and Tregs) and B cells subsets (naïve, unswitched memory, switched memory and transitional B cells) were analysed in peripheral blood of adult T1D patients at disease onset and after ≥2 years using multiparametric flow cytometry. Here we report changes in the percentage of early and late effector memory CD4+ and CD8+ T cells as well as of naïve subsets, regulatory T cells and transitional B cells in peripheral blood of adult patients at onset of T1D when compared with HD. After 2 years follow-up these changes were maintained. Also, we found a decrease in percentage of Th17 and numbers of T cells with baseline. In order to identify potential biomarkers of disease, ROC curves were performed being late EM CD4 T cell subset the most promising candidate. In conclusion, the observed changes in the percentage and/or absolute number of lymphocyte subpopulations of adult T1D patients support the hypothesis that effector cells migrate to the pancreas and this autoimmune process perseveres along the disease. Moreover, multiparametric flow allows to identify those subsets with potential to be considered biomarkers of disease.

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Section: Discussionsupporting

confidence: 58%

Identifying Changes in Peripheral Lymphocyte Subpopulations in Adult Onset Type 1 Diabetes

et al. 2021

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“…It is clear that subsets, such as transitional CD24 hi CD38 hi B cells, enriched with IL-10 + B cells, decline with age ( 27 , 57 ), which is an important note for future studies. Recently, in children with type 1 diabetes, a decrease in both the CD24 hi CD27 + (B10) and transitional CD24 hi CD38 hi IL-10 + B cells but not in CD38 hi CD27 + IL-10 + plasmablasts was found ( 31 ). This numerical decrease was also negatively correlated with HbA1c levels ( 31 ), as was the frequency of CD24 hi CD38 hi B cells in a study by Wang et al.…”

Section: Impaired Regulatory B Cell Mechanisms In Type 1 Diabetesmentioning

confidence: 99%

“…Recently, in children with type 1 diabetes, a decrease in both the CD24 hi CD27 + (B10) and transitional CD24 hi CD38 hi IL-10 + B cells but not in CD38 hi CD27 + IL-10 + plasmablasts was found ( 31 ). This numerical decrease was also negatively correlated with HbA1c levels ( 31 ), as was the frequency of CD24 hi CD38 hi B cells in a study by Wang et al. ( 30 ).…”

Section: Impaired Regulatory B Cell Mechanisms In Type 1 Diabetesmentioning

confidence: 99%

Regulatory B Cells: Role in Type 1 Diabetes

Boldison

Wong

2021

Front. Immunol.

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Regulatory B cells (Bregs) have an anti-inflammatory role and can suppress autoimmunity, by employing both cytokine secretion and cell-contact mediated mechanisms. Numerous Breg subsets have been described and have overlapping phenotypes in terms of their immune expression markers or cytokine production. A hallmark feature of Bregs is the secretion of IL-10, although IL-35 and TGFβ−producing B cells have also been identified. To date, few reports have identified an impaired frequency or function of Bregs in individuals with type 1 diabetes; thus our understanding of the role played by these Breg subsets in the pathogenesis of this condition is limited. In this review we will focus on how regulatory B cells are altered in the development of type 1 diabetes, highlighting both frequency and function and discuss both human and animal studies.

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“…A recent report from Sha et al revealed that IL-10-producing B cells prevent the development of diabetes in NOD mice via depleting the toll-like receptor 9 (TLR9) pathway [ 21 ]. In addition, El-Mokhtar et al reported lowered percentages of IL-10 + Breg cells in children with T1D [ 22 ]. Kleffel S et al reported an increase in IL-10 + Breg cells in the CD40 + B cells compartment that prevents β-cell destruction in NOD mice [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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

Luo

Lundin

Mejia-Cordova

et al. 2021

IJMS

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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.

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Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus

Cited by 17 publications

References 38 publications

Identifying Changes in Peripheral Lymphocyte Subpopulations in Adult Onset Type 1 Diabetes

Identifying Changes in Peripheral Lymphocyte Subpopulations in Adult Onset Type 1 Diabetes

Regulatory B Cells: Role in Type 1 Diabetes

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

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