Heterogeneous subsets of B-lineage regulatory cells (Breg cells)

Baba, Yoshifumi; Saito, Yuichi; Kotetsu, Yasuaki

doi:10.1093/intimm/dxz068

Cited by 39 publications

(34 citation statements)

References 95 publications

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“…Indeed, Tregs have been shown to act in synergy with Bregs to promote immune tolerance. Bregs compose a specific B cell subtype that produces the anti-inflammatory cytokines IL-10 and/or IL-35 ( 38 – 41 ). They have been found to synthesize allergen-specific IgG4 in AIT treated patients ( 42 , 43 ).…”

Section: Introductionmentioning

confidence: 99%

CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance

et al. 2021

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Prevalence and incidence of IgE-mediated allergic diseases have increased over the past years in developed and developing countries. Allergen-specific immunotherapy (AIT) is currently the only curative treatment available for allergic diseases that has long-term efficacy. Although AIT has been proven successful as an immunomodulatory therapy since its beginnings, it still faces several unmet needs and challenges today. For instance, some patients can experience severe side effects, others are non-responders, and prolonged treatment schedules can lead to lack of patient adherence and therapy discontinuation. A common strategy to improve AIT relies on the use of adjuvants and immune modulators to boost its effects and improve its safety. Among the adjuvants tested for their clinical efficacy, CpG oligodeoxynucleotide (CpG-ODN) was investigated with limited success and without reaching phase III trials for clinical allergy treatment. However, recently discovered immune tolerance-promoting properties of CpG-ODN place this adjuvant again in a prominent position as an immune modulator for the treatment of allergic diseases. Indeed, it has been shown that the CpG-ODN dose and concentration are crucial in promoting immune regulation through the recruitment of pDCs. While low doses induce an inflammatory response, high doses of CpG-ODN trigger a tolerogenic response that can reverse a pre-established allergic milieu. Consistently, CpG-ODN has also been found to stimulate IL-10 producing B cells, so-called B regulatory cells (Bregs). Accordingly, CpG-ODN has shown its capacity to prevent and revert allergic reactions in several animal models showing its potential as both preventive and active treatment for IgE-mediated allergy. In this review, we describe how CpG-ODN-based therapies for allergic diseases, despite having shown limited success in the past, can still be exploited further as an adjuvant or immune modulator in the context of AIT and deserves additional attention. Here, we discuss the past and current knowledge, which highlights CpG-ODN as a potential adjuvant to be reevaluated for the enhancement of AIT when used in appropriate conditions and formulations.

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Section: Introductionmentioning

confidence: 99%

CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance

et al. 2021

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“…They demonstrated that the interleukin-10 (IL-10)-producing CD1d + Bregs were induced in a chronic inflammatory environment and dampened the progression of intestinal inflammation by repressing inflammatory cascades associated with IL-1 upregulation and STAT3 activation. Thereafter, mounting evidence has uncovered the roles of Bregs in numerous diseases and conditions, such as infection (16), allergies (17), autoimmune diseases (18), transplantation (19), and tumors (20).…”

Section: Introductionmentioning

confidence: 99%

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

Shang

Zha²,

Sun

2020

Front. Immunol.

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In immune system, B cells are classically positive modulators that regulate inflammation and immune responses. Regulatory B cells (Bregs) are a subset of B cells which play crucial roles in various conditions, including infection, allergies, autoimmune diseases, transplantation, and tumors. Until now, unequivocal surface markers for Bregs still lack consensus, although numerous Breg subsets have been identified. Generally, Bregs exert their immunoregulatory functions mainly through cytokine secretion and intercellular contact. In the tumor microenvironment, Bregs suppress effector T cells, induce regulatory T cells and target other tumor-infiltrating immune cells, such as myeloidderived suppressor cells, natural killer cells and macrophages, to hamper anti-tumor immunity. Meanwhile, the cross-regulations between Bregs and tumor cells often result in tumor escape from immunosurveillance. In addition, accumulating evidence suggests that Bregs are closely associated with many clinicopathological factors of cancer patients and might be potential biomarkers for accessing patient survival. Thus, Bregs are potential therapeutic targets for future immunotherapy in cancer patients. In this review, we will discuss the phenotypes, functions, and clinical relevance of Bregs in cancer.

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“…These phenomena are the result of the infiltration of lymphocytes into the synovium and the production of collagen-specific IgG autoantibodies by B cells (4). Recently, a new subset of B cells termed regulatory B cells (Breg cells) were identified that can secrete interleukin-10 (IL-10) to inhibit the production of proinflammatory cytokines and restrain excessive immune responses (5,6). The adoptive transfer of Breg cells has been reported to suppress the development of arthritis (7).…”

Section: Introductionmentioning

confidence: 99%

Granulocytic Myeloid-Derived Suppressor Cell Exosomal Prostaglandin E2 Ameliorates Collagen-Induced Arthritis by Enhancing IL-10+ B Cells

Zhu

Tian

et al. 2020

Front. Immunol.

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The results of recent studies have shown that granulocytic-myeloid derived suppressor cells (G-MDSCs) can secrete exosomes that transport various biologically active molecules with regulatory effects on immune cells. However, their roles in autoimmune diseases such as rheumatoid arthritis remain to be further elucidated. In the present study, we investigated the influence of exosomes from G-MDSCs on the humoral immune response in murine collagen-induced arthritis (CIA). G-MDSCs exosomes-treated mice showed lower arthritis index values and decreased inflammatory cell infiltration. Treatment with G-MDSCs exosomes promoted splenic B cells to secrete IL-10 both in vivo and in vitro. In addition, a decrease in the proportion of plasma cells and follicular helper T cells was observed in drainage lymph nodes from G-MDSCs exosomes-treated mice. Moreover, lower serum levels of IgG were detected in G-MDSCs exosomes-treated mice, indicating an alteration of the humoral environment. Mechanistic studies showed that exosomal prostaglandin E2 (PGE2) produced by G-MDSCs upregulated the phosphorylation levels of GSK-3β and CREB, which play a key role in the production of IL-10+ B cells. Taken together, our findings demonstrated that G-MDSC exosomal PGE2 attenuates CIA in mice by promoting the generation of IL-10+ Breg cells.

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Heterogeneous subsets of B-lineage regulatory cells (Breg cells)

Cited by 39 publications

References 95 publications

CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance

CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

Granulocytic Myeloid-Derived Suppressor Cell Exosomal Prostaglandin E2 Ameliorates Collagen-Induced Arthritis by Enhancing IL-10+ B Cells

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