scholarly journals Regulatory B Cells: Role in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Joanne Boldison ◽  
F. Susan Wong
Keyword(s):  
Type 1 Diabetes ◽  
B Cells ◽  
Animal Studies ◽  
Cytokine Production ◽  
Cytokine Secretion ◽  
Cell Contact ◽  
Regulatory B Cells ◽  
And Function ◽  
Hallmark Feature

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.

scholarly journals TLR9-deficiency in B cells Promotes Immune Tolerance via IL-10 in a Type 1 Diabetes Mouse Model

2020 ◽  
Author(s):  
Ada Admin ◽  
Sha Sha ◽  
James A Pearson ◽  
Jian Peng ◽  
Youjia Hu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
B Cells ◽  
B Cell ◽  
Nod Mice ◽  
Adaptive Immune ◽  
Immune Molecule ◽  
And Function ◽  
Intrinsic Effect ◽  
Specific Deletion

Toll-like receptor 9 (TLR9) is highly expressed in B cells and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on beta cell autoimmunity is not known. To fill this knowledge gap, we generated non-obese diabetic (NOD) mice with a B cell-specific deficiency of TLR9 (TLR9<sup>fl/fl</sup>/CD19-Cre+ NOD). The B cell-specific deletion of TLR9 resulted in near complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of IL-10-producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune-stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10-producing B cells. Molecular analysis revealed a network of TLR9 with MMPs, TIMP1 and CD40, all of which are inter-connected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immuno-pathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.

scholarly journals TLR9-deficiency in B cells Promotes Immune Tolerance via IL-10 in a Type 1 Diabetes Mouse Model

2020 ◽  
Author(s):  
Ada Admin ◽  
Sha Sha ◽  
James A Pearson ◽  
Jian Peng ◽  
Youjia Hu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
B Cells ◽  
B Cell ◽  
Nod Mice ◽  
Adaptive Immune ◽  
Immune Molecule ◽  
And Function ◽  
Intrinsic Effect ◽  
Specific Deletion

Toll-like receptor 9 (TLR9) is highly expressed in B cells and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on beta cell autoimmunity is not known. To fill this knowledge gap, we generated non-obese diabetic (NOD) mice with a B cell-specific deficiency of TLR9 (TLR9<sup>fl/fl</sup>/CD19-Cre+ NOD). The B cell-specific deletion of TLR9 resulted in near complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of IL-10-producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune-stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10-producing B cells. Molecular analysis revealed a network of TLR9 with MMPs, TIMP1 and CD40, all of which are inter-connected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immuno-pathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.

scholarly journals TLR9-Deficiency in B Cells Promotes Immune Tolerance via IL-10 in a Type 1 Diabetes Mouse Model

Diabetes ◽  
2020 ◽  
pp. db200373
Author(s):  
Sha Sha ◽  
James A Pearson ◽  
Jian Peng ◽  
Youjia Hu ◽  
Juan Huang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
B Cells ◽  
Mouse Model ◽  
Immune Tolerance ◽  
Diabetes Mouse

scholarly journals Immunosuppressive Mechanisms of Regulatory B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Catalán ◽  
Miguel Andrés Mansilla ◽  
Ashley Ferrier ◽  
Lilian Soto ◽  
Kristine Oleinika ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
Surface Proteins ◽  
Regulatory B Cells ◽  
Cell Surface Proteins ◽  
The Past ◽  
And Function

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

scholarly journals Rodent Models for Investigating the Dysregulation of Immune Responses in Type 1 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Feng-Cheng Chou ◽  
Heng-Yi Chen ◽  
Shyi-Jou Chen ◽  
Mei-Cho Fang ◽  
Huey-Kang Sytwu
Keyword(s):  
Type 1 Diabetes ◽  
Animal Studies ◽  
Genetic Manipulation ◽  
Nod Mice ◽  
Environmental Parameters ◽  
Conditional Knockout ◽  
Therapeutic Approaches ◽  
Nonobese Diabetic ◽  
Genetically Manipulated

Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells that selectively destroy the insulin-producingβcells. Previous reports based on epidemiological and animal studies have demonstrated that both genetic factors and environmental parameters can either promote or attenuate the progression of autoimmunity. In recent decades, several inbred rodent strains that spontaneously develop diabetes have been applied to the investigation of the pathogenesis of T1D. Because the genetic manipulation of mice is well developed (transgenic, knockout, and conditional knockout/transgenic), most studies are performed using the nonobese diabetic (NOD) mouse model. This paper will focus on the use of genetically manipulated NOD mice to explore the pathogenesis of T1D and to develop potential therapeutic approaches.

Physical Activity and Nerve Structure and Function in Patients With Longstanding Type 1 Diabetes

2021 ◽  
Vol 45 (7) ◽  
pp. S7
Author(s):  
Evan Lewis ◽  
Leif Erik Lovblom ◽  
Sebastien Lanctot ◽  
Daniel Scarr ◽  
Vera Bril ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 1 Diabetes ◽  
Structure And Function ◽  
Nerve Structure ◽  
And Function

scholarly journals Distinct Roles of β-Cell Mass and Function During Type 1 Diabetes Onset and Remission

Diabetes ◽  
2015 ◽  
Vol 64 (6) ◽  
pp. 2148-2160 ◽  
Author(s):  
Helena Chmelova ◽  
Christian M. Cohrs ◽  
Julie A. Chouinard ◽  
Cathleen Petzold ◽  
Matthias Kuhn ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Mass ◽  
Β Cell ◽  
Diabetes Onset ◽  
And Function

scholarly journals Potential Role for Regulatory B Cells as a Major Source of Interleukin-10 in Spleen fromPlasmodium chabaudi-Infected Mice

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Xue Han ◽  
Ji Yang ◽  
Yitong Zhang ◽  
Yalin Zhang ◽  
Hongtao Cao ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Potential Role ◽  
Interleukin 10 ◽  
Surface Markers ◽  
Regulatory B Cells ◽  
Plasmodium Chabaudi ◽  
Impact On Survival ◽  
And Function ◽  
Stimulation Of

ABSTRACTInterleukin-10 (IL-10)-producing regulatory B (Breg) cells were found to be induced in a variety of infectious diseases. However, its importance in the regulation of immune response to malaria is still unclear. Here, we investigated the dynamics, phenotype, and function of Breg cells usingPlasmodium chabaudi chabaudiAS-infected C57BL/6 and BALB/c mice. BALB/c mice were more susceptible to infection and had a stronger IL-10 response in spleen than C57BL/6 mice. Analysis of the surface markers of IL-10-producing cells with flow cytometry showed that CD19+B cells were one of the primary IL-10-producing populations inP. c. chabaudiAS-infected C57BL/6 and BALB/c mice, especially in the latter one. The Breg cells had a heterogeneous phenotype which shifted during infection. The well-established Breg subset, CD19+CD5+CD1dhicells, accounted for less than 20% of IL-10-producing B cells in both strains during the course of infection. Most Breg cells were IgG+and CD138−from day 0 to day 8 postinfection. Adoptive transfer of Breg cells to C57BL/6 mice infected withP. c. chabaudiAS led to a transient increase of parasitemia without an impact on survival rate. Our finding reveals that B cells play an active and important regulatory role in addition to mediating humoral immunity in immune response against malaria, which should be paid more attention in developing therapeutic or vaccine strategies against malaria involving stimulation of B cells.

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