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Shirou Fukuhara - One of the best experts on this subject based on the ideXlab platform.

  • immunomodulatory effects of cyclosporin a on human peripheral Blood Dendritic Cell subsets
    Immunology, 2003
    Co-Authors: Kenichirou Tajima, Ryuichi Amakawa, Tomoki Ito, Michihiko Miyaji, Masashi Takebayashi, Shirou Fukuhara
    Abstract:

    Cyclosporin A (CsA) is a potent immuno-suppressant and is approved for the treatment of various disease conditions. The molecular biological mechanism of CsA has been investigated intensively in T Cells and has been shown to involve the intraCellular calcineurin pathway. Recently, it was reported that CsA has capacities to affect not only T Cells but also antigen-presenting Cells such as B Cells and Dendritic Cells (DCs). DCs are a master regulator of immune responses that have an integral capacity to prime naive T Cells. In the present study, we investigated the biological effects of CsA on human peripheral Blood DC subsets: CD11c+ myeloid and CD11c- lymphoid subsets. CsA inhibited the up-regulation of co-stimulatory molecules induced with or without microbial stimuli and CD40L on both CD11c+ and CD11c- subsets. In addition, CsA negatively regulated the endocytic activity of CD11c+ DC during the immature state. CsA inhibited the interleukin-12 (IL-12) production, but augmented the IL-10 production from the LPS-stimulated CD11c+ subset, whereas CsA reduced the interferon-alpha (IFN-alpha) production from the CD11c- subset infected with Sendai virus (SV). Both the LPS-stimulated CD11c+ subset and SV-infected CD11c- subset preferentially induced the development of IFN-gamma-producing T helper-type 1 (Th1) Cells. Pretreatment of these DC subsets with CsA inhibited the Th1 skewing. These findings suggested a DC-mediated mechanism of immunosuppression by CsA.

  • interferon α and interleukin 12 are induced differentially by toll like receptor 7 ligands in human Blood Dendritic Cell subsets
    Journal of Experimental Medicine, 2002
    Co-Authors: Ryuichi Amakawa, Hideyuki Tomizawa, Tsuneyasu Kaisho, Hiroaki Hemmi, Kenichirou Tajima, Kazutaka Uehira, Yoshio Ozaki, Shirou Fukuhara
    Abstract:

    Dendritic Cells (DCs) play a crucial role in the immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). In humans, two distinct DC subsets, CD11c− plasmacytoid DCs (PDCs) and CD11c+ myeloid DCs (MDCs), have been identified and can respond to different TLR ligands, depending on the differential expression of cognate TLRs. In this study, we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival of the subsets and upregulated the surface expression of costimulatory molecules such as CD40, CD80, and CD86. However, the cytokine induction pattern was distinct in that PDCs and MDCs produced interferon (IFN)-α and interleukin (IL)-12, respectively. In response to TLR-7 ligands, the Th1 Cell supporting ability of both DC subsets was enhanced, depending on the cytokines the respective subsets produced. This study demonstrates that TLR-7 exerts its biological effect in a DC subset-specific manner.

  • differential regulation of human Blood Dendritic Cell subsets by ifns
    Journal of Immunology, 2001
    Co-Authors: Tomoki Ito, Ryuichi Amakawa, Muneo Inaba, Susumu Ikehara, Kayo Inaba, Shirou Fukuhara
    Abstract:

    Based on the relative expression of CD11c and CD1a, we previously identified subsets of Dendritic Cells (DCs) or DC precursors in human peripheral Blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans Cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing Cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral Blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T Cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10-producing regulatory T Cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T Cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3-primed CD11c(-) DCs activated T Cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.

Juno Jin - One of the best experts on this subject based on the ideXlab platform.

  • comparison of human peripheral Blood Dendritic Cell activation by four fucoidans
    International Journal of Biological Macromolecules, 2021
    Co-Authors: Wei Zhang, Haebin Park, Juyoung Hwang, Juno Jin, Dhananjay Yadav, Heeyun Eom, Sojung Kim, Minseok Kwak, Peter C W Lee
    Abstract:

    Brown seaweed is an important source of fucoidan, which displays immunomodulatory effects by activating various immune Cells. However, these effects of fucoidans from various sources of brown seaweed have not yet been explored in human Blood Dendritic Cells. We studied fucoidans extracted from Ecklonia cava, Macrocystis pyrifera, Undaria pinnatifida, and Fucus vesiculosus for their effects on human monocyte-derived Dendritic Cells (MODC) and human peripheral Blood DC (PBDC) activation. Ecklonia cava fucoidan (ECF) strongly upregulated co-stimulatory molecules, major histocompatibility complex class I and II, and the production of proinflammatory cytokines in MODCs and PBDCs compared to those by the other three fucoidans. Moreover, ECF elicited the strongest effect in the induction of syngeneic T Cell proliferation and IFN-γ production compared to those of other fucoidans. These results suggest that ECF could be a suitable candidate molecule for enhancing immune activation in humans compared to that with the other three fucoidans.

  • human peripheral Blood Dendritic Cell and t Cell activation by codium fragile polysaccharide
    Marine Drugs, 2020
    Co-Authors: Wei Zhang, Sangguan You, Haebin Park, Seongmin Lim, Juyoung Hwang, Jihoe Kim, Inho Choi, Juno Jin
    Abstract:

    Natural polysaccharides exhibit an immunostimulatory effect with low toxicity in humans and animals. It has shown that polysaccharide extracted from Codium fragile (CFP) induces anti-cancer immunity by Dendritic Cell (DC) activation, while the effect of CFP has not examined in the human immune Cells. In this study, we found that CFP promoted the upregulation of CD80, CD83 and CD86 and major histocompatibility complex (MHC) class I and II in human monocyte-derived Dendritic Cells (MDDCs). In addition, CFP induced the production of proinflammatory cytokines in MDDCs. Moreover, CFP directly induced the activation of Blood Dendritic Cell Antigen (BDCA)1+ and BDCA3+ subsets of human peripheral Blood DCs (PBDCs). The CFP-stimulated BDCA1+ PBDCs further promoted activation and proliferation of syngeneic CD4 T Cells. The CFP-activated BDCA3+ PBDCs activated syngeneic CD8 T Cells, which produced cytotoxic mediators, namely, cytotoxic T lymphocytes. These results suggest that CFP may be a candidate molecule for enhancing immune activation in humans.

Mirjam H. M. Heemskerk - One of the best experts on this subject based on the ideXlab platform.

  • Clinically applicable CD34^+-derived Blood Dendritic Cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK Cell responses
    Cancer Immunology Immunotherapy, 2021
    Co-Authors: Jesper Van Eck Van Der Sluijs, Diede Van Ens, Soley Thordardottir, Denise Vodegel, Inge Hermens, Anniek B. Van Der Waart, J. H. Frederik Falkenburg, Michel G. D. Kester, Iris De Rink, Mirjam H. M. Heemskerk
    Abstract:

    Allogeneic stem Cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, Dendritic Cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human Blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34^+ hematopoietic progenitor Cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo Blood counterparts. In more detail, we demonstrated that the CD141^+CLEG9A^+ cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF- α . Furthermore, cDC1s efficiently primed alloreactive T Cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T Cells. Moreover, they strongly enhanced NK Cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional Blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients.

Malin Lindstedt - One of the best experts on this subject based on the ideXlab platform.

  • human Blood Dendritic Cell subsets exhibit discriminative pattern recognition receptor profiles
    Immunology, 2014
    Co-Authors: Kristina Lundberg, Frida Rydnert, Lennart Greiff, Malin Lindstedt
    Abstract:

    Dendritic Cells (DCs) operate as the link between innate and adaptive immunity. Their expression of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), enables antigen recognition and mediates appropriate immune responses. Distinct subsets of human DCs have been identified; however their expression of PRRs is not fully clarified. Expressions of CLRs by DC subpopulations, in particular, remain elusive. This study aimed to identify and compare PRR expressions on human Blood DC subsets, including CD1c(+) , CD141(+) and CD16(+) myeloid DCs and CD123(+) plasmacytoid DCs, in order to understand their capacity to recognize different antigens as well as their responsiveness to PRR-directed targeting. Whole Blood was obtained from 13 allergic and six non-allergic individuals. Mononuclear Cells were purified and multi-colour flow cytometry was used to assess the expression of 10 CLRs and two TLRs on distinct DC subsets. PRR expression levels were shown to differ between DC subsets for each PRR assessed. Furthermore, principal component analysis and random forest test demonstrated that the PRR profiles were discriminative between DC subsets. Interestingly, CLEC9A was expressed at lower levels by CD141(+) DCs from allergic compared with non-allergic donors. The subset-specific PRR expression profiles suggests individual responsiveness to PRR-targeting and supports functional specialization.

  • fc epsilon ri levels and frequencies of peripheral Blood Dendritic Cell populations in allergic rhinitis
    Human Immunology, 2010
    Co-Authors: Kristina Lundberg, Lennart Greiff, Carl A K Borrebaeck, Malin Lindstedt
    Abstract:

    The Dendritic Cell (DC) lineage encompasses a diverse population of Cells with unique subtype-specific functions. In peripheral Blood, four DC subsets have been identified based on their distinct expression of CD1c, CD141, CD16, and CD123, and these subpopulations exhibit functional properties in immune responses. However, their respective roles in allergic diseases, such as rhinitis, are unclear. In this study, we have performed comparative assessments of DC subset frequencies and investigated their Fc epsilon RI expression levels in patients with allergic rhinitis. We demonstrate that the frequencies of CD1c(+) and CD141(+) DCs are elevated in grass pollen-allergic subjects compared with healthy controls, irrespectively of allergen stimulation. Among the DC subsets, CD1c(+) DCs expressed the highest levels of Fc epsilon RI mRNA, and a large proportion expressed surface Fc epsilon RI. Furthermore, the Fc epsilon RI expression levels were augmented upon allergen challenge. Thus our data suggest that CD1c(+) DCs influence allergen-specific immune responses. Research on their functional properties in allergy is warranted for development of future immunotherapies targeting specialized DC subsets. (C) 2010 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and immunogenetics. (Less)

Alix Baugier De Materre - One of the best experts on this subject based on the ideXlab platform.

  • blastic plasmacytoid Dendritic Cell neoplasm from origin of the Cell to targeted therapies
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Kamel Laribi, Nathalie Denizon, Anne Besancon, Jonathan Farhi, Pierre Lemaire, Jeremy Sandrini, Catherine Truong, Habib Ghnaya, Alix Baugier De Materre
    Abstract:

    Abstract Blastic plasmacytoid Dendritic Cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia–related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral Blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem Cell transplantation may improve survival. This neoplasm is derived from precursors of plasmacytoid Dendritic Cells and is characterized by the coexpression of the immunophenotypic markers CD4, CD56, CD123, Blood Dendritic Cell antigen-2, Blood Dendritic Cell antigen-4, CD2AP, and lineage−. Atypical immunophenotype expression may be present, making diagnosis difficult. BPDCN is often associated with a complex karyotype, frequent deletions of tumor suppressor genes, and mutations affecting either the DNA methylation or chromatin remodeling pathways. A better understanding of the etiology and pathophysiology of this neoplasm could open the way to new therapies targeting specific signaling pathways or involving epigenetics.