• Title/Summary/Keyword: Regulatory B cells

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Presence of Foxp3-expressing CD19(+)CD5(+) B Cells in Human Peripheral Blood Mononuclear Cells: Human CD19(+)CD5(+)Foxp3(+) Regulatory B Cell (Breg)

  • Noh, Joon-Yong;Choi, Wahn-Soo;Noh, Geun-Woong;Lee, Jae-Ho
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.247-249
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    • 2010
  • Foxp3 is a transcript factor for regulatory T cell development. Interestingly, Foxp3-expressing cells were identified in B cells, especially in CD19(+)CD5(+) B cells, while those were not examined in CD19(+)CD5(-) B cells. Foxp3-expressing CD5(+) B cells in this study were identified in human PBMCs and were found to consist of $8.5{\pm}3.5%$ of CD19(+)CD5(+) B cells. CD19(+)CD5(+)Foxp3(+) B cells showed spontaneous apoptosis. Rare CD19(+)CD5(+) Foxp3(+) regulatory B cell (Breg) population was unveiled in human peripheral blood mononuclear cells and suggested as possible regulatory B cells (Breg) as regulatory T cells (Treg). The immunologic and the clinical relevant of Breg needs to be further investigated.

Regulatory T Cells in B Cell Follicles

  • Chang, Jae-Hoon;Chung, Yeonseok
    • IMMUNE NETWORK
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    • v.14 no.5
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    • pp.227-236
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    • 2014
  • Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation $(CD)8^+$ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.

JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF-κB axis

  • Lee, Min Bum;Lee, Jun-Ho;Hong, Seong Hwi;You, Jueng Soo;Nam, Seung Taek;Kim, Hyun Woo;Park, Young Hwan;Lee, Dajeong;Min, Keun Young;Park, Yeong-Min;Kim, Young Mi;Kim, Hyuk Soon;Choi, Wahn Soo
    • BMB Reports
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    • v.50 no.12
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    • pp.640-646
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    • 2017
  • Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells. While bromodomain-containing protein 4 (BRD4) was associated with $NF-{\kappa}B$ on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with $NF-{\kappa}B$ on IL-10 promoter. In summary, BRD4 is essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting JQ1 could be a potential candidate in regulating IL-10-producing regulatory B cells in cancer.

Interleukin-10-Producing B Cells Help Suppress Ovariectomy-Mediated Osteoporosis

  • Yuhua Wang;Wei Zhang;Seong-Min Lim;Li Xu;Jun-O Jin
    • IMMUNE NETWORK
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    • v.20 no.6
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    • pp.50.1-50.11
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    • 2020
  • Osteoporosis is prevalent in elderly women and it may cause dental implant failure. In particular, estrogen deficiency in postmenopausal women leads to higher rates of osteoporosis prevalence. Immune cell-mediated effects involving the development of osteoporosis have been studied previously; however, the role of IL-10-producing regulatory B (B10) cells in osteoporosis is largely unclear. Here, we examined the role of B10 cells in osteoporosis. C57BL/6 mice were subjected to ovariectomy (OVX). Fifteen weeks after OVX surgery, the first molar of the right maxillary was extracted, and twenty-four weeks after OVX surgery, serous progression of osteoporosis was observed in the alveolar bone. Moreover, the proportion of CD19+CD5+CD1dhigh regulatory B cells, B10, and CD4+CD25+FoxP3+ regulatory T cells from the spleen of OVX mice decreased during the progression of osteoporosis, compared to controls. In contrast to regulatory cells, IL-17-producing Th (Th17) cell levels were increased in OVX mice. Adoptive transfer of B10 cells to OVX mice led to a decrease in Th17 cell abundance and inhibited the development of osteoporosis in the alveolar bone from OVX mice. Thus, our results suggest that B10 cells may help suppress osteoporosis development.

Induction of CD4+ Regulatory and Polarized Effector/helper T Cells by Dendritic Cells

  • Manfred B. Lutz
    • IMMUNE NETWORK
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    • v.16 no.1
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    • pp.13-25
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    • 2016
  • Dendritic cells (DCs) are considered to play major roles during the induction of T cell immune responses as well as the maintenance of T cell tolerance. Naive CD4+ T cells have been shown to respond with high plasticity to signals inducing their polarization into effector/helper or regulatory T cells. Data obtained from in vitro generated bone-marrow (BM)-derived DCs as well as genetic mouse models revealed an important but not exclusive role of DCs in shaping CD4+ T cell responses. Besides the specialization of some conventional DC subsets for the induction of polarized immunity, also the maturation stage, activation of specialized transcription factors and the cytokine production of DCs have major impact on CD4+ T cells. Since in vitro generated BM-DCs show a high diversity to shape CD4+ T cells and their high similarity to monocyte-derived DCs in vivo, this review reports data mainly on BM-DCs in this process and only touches the roles of transcription factors or of DC subsets, which have been discussed elsewhere. Here, recent findings on 1) the conversion of naive into anergic and further into Foxp3- regulatory T cells (Treg) by immature DCs, 2) the role of RelB in steady state migratory DCs (ssmDCs) for conversion of naive T cells into Foxp3+ Treg, 3) the DC maturation signature for polarized Th2 cell induction and 4) the DC source of IL-12 for Th1 induction are discussed.

Comparison Analysis of Immune Cells between CT26 Tumor Bearing Mice and Normal Mice

  • Lee, Na Kyung;Kim, Hong Sung
    • Biomedical Science Letters
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    • v.20 no.3
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    • pp.147-155
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    • 2014
  • It has well studied that immune cells are strongly related to tumor progression and tumor suppression. To identify the difference of immune cell between tumor bearing mice and normal mice, we examined systemically the immune cell of CT26 tumor bearing mice on 21 days after tumor cell administration. As previously reported, CD4+ and CD8+ T cells population of tumor bearing mice significantly decreased 38% and 30% on day 21 compared to that of normal mice, respectively. All subpopulation of CD4 and CD8+ T cell significantly decreased, except CD49b+ T cell subpopulation. But, myeloid cell population ($CD11b^{high}$ and all Gr-1+ subpopulation) of tumor bearing mice significantly increased on day 21. Especially, all subpopulation of CD11b+Gr-1+ cell of tumor bearing mice significantly increased on day 21. Also, Foxp3+$CD25^{high}$ CD4 T cell (regulatory T cells) population significantly increased on day 21. These results suggest that tumor can induce the decline of T lymphocyte and the expansion of myeloid cells and regulatory T cells, and provide the basic information for the study of tumor immunology.

Germinal Center Formation Controlled by Balancing Between Follicular Helper T Cells and Follicular Regulatory T Cells (여포 보조 T세포와 여포 조절 T세포의 균형 및 종자중심 형성)

  • Park, Hong-Jai;Kim, Do-Hyun;Choi, Je-Min
    • Hanyang Medical Reviews
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    • v.33 no.1
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    • pp.10-16
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    • 2013
  • Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

Entinostat, a histone deacetylase inhibitor, increases the population of IL-10+ regulatory B cells to suppress contact hypersensitivity

  • Min, Keun Young;Lee, Min Bum;Hong, Seong Hwi;Lee, Dajeong;Jo, Min Geun;Lee, Ji Eon;Choi, Min Yeong;You, Jueng Soo;Kim, Young Mi;Park, Yeong Min;Kim, Hyuk Soon;Choi, Wahn Soo
    • BMB Reports
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    • v.54 no.10
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    • pp.534-539
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    • 2021
  • IL-10+ regulatory B (Breg) cells play a vital role in regulating the immune responses in experimental autoimmune encephalomyelitis, colitis, and contact hypersensitivity (CHS). Several stimulants such as lipopolysaccharide (LPS), CD40 ligand, and IL-21 spur the activation and maturation of IL-10+ Breg cells, while the epigenetic mechanism for the IL-10 expression remains largely unknown. It is well accepted that the histone acetylation/deacetylation is an important mechanism that regulates the expression of IL-10. We found that entinostat, an HDAC inhibitor, stimulated the induction of IL-10+ Breg cells by LPS in vitro and the formation of IL-10+ Breg cells to suppress CHS in vivo. We further demonstrated that entinostat inhibited HDAC1 from binding to the proximal region of the IL-10 expression promoter in splenic B cells, followed by an increase in the binding of NF-κB p65, eventually enhancing the expression of IL-10 in Breg cells.

Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing Crosstalk between Reactive Oxygen Species and NF-κB

  • Prasad, Rajapaksha Gedara;Choi, Yung Hyun;Kim, Gi-Young
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.110-118
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    • 2015
  • According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-${\kappa}B$ (TNF-${\alpha}$) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-${\alpha}$ in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-${\alpha}$, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, $PGE_2$, and TNF-${\alpha}$ in LPS-treated BV2 microglial cells by suppressing ROS and NF-${\kappa}B$. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-${\kappa}B$ signaling pathway.

The Roles of Immune Regulatory Factors FoxP3, PD-1, and CTLA-4 in Chronic Viral Infection (만성 바이러스 감염에서 면역조절인자 FoxP3, PD-1 및 CTLA-4의 역할)

  • Cho, Hyosun
    • Korean Journal of Microbiology
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    • v.49 no.3
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    • pp.221-227
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    • 2013
  • Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) cause viral infections that lead to chronic diseases. When they invade human body, virus specific T cells play an important role in antiviral effector functions including killing virus-infected cells and helping B cells to produce specific antibodies against viral proteins. The antiviral activity of T cells is usually affected by immune-regulatory factors that express on surface of T cells. Recently, many researchers have investigated the relationship between effector functions of virus specific T cells and characteristics of immune regulatory factors (e.g., CD28, CD25, CD45RO, FoxP3, PD-1, CTLA-4). In particular, Immune inhibitory molecules such as forkhead box P3 (FoxP3), programmed death-1 (PD-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with T-cell dysfunction. They are shown to be up-regulated in chronic viral diseases such as hepatitis B, hepatitis C or human immunodeficiency virus infection. Therefore, the positive correlation between viral persistence and expression of immune regulatory factors (FoxP3, PD-1, and CTLA-4) has been suggested. In this review, the roles of immune regulatory factors FoxP3, PD-1, and CTLA-4 were discussed in chronic viral diseases such as HIV, HBV, or HCV.