CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease

Hadeiba, Husein; Sato, Tohru; Habtezion, Aida; Oderup, Cecilia; Pan, Junliang; Butcher, Eugene C.

doi:10.1038/ni.1658

Cited by 274 publications

(289 citation statements)

References 55 publications

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“…A subset of host pDCs that express the CCR9 receptor can suppress GVHD. 31 However, host pDCs have been shown to induce GVHD in a TLR-independent manner. 32 In addition, GVHD prevents the maturation of donor pDCs.…”

Section: Sensors Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

158

126

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The use of allogeneic hematopoietic cell transplantation (HCT) has increased as new techniques have been developed for transplantation in patients who previously would not have been considered HCT candidates. However, its efficacy continued to be limited by the development of frequent and severe acute GVHD. The complex and intricate pathophysiology of acute GVHD is a consequence of interactions between the donor and host innate and adaptive immune responses. Multiple inflammatory molecules and cell types are implicated in the development of GVHD that can be categorized as:(1) triggers that initiate GVHD by therapy-induced tissue damage and the antigen disparities between host and graft tissue; (2) sensors that detect the triggers, that is, process and present alloantigens; (3) mediators such as T-cell subsets (naive, memory, regulatory, Th17 and natural killer T cells) and (4) the effectors and amplifiers that cause damage of the target organs. These multiple inflammatory molecules and cell types that are implicated in the development of GVHD have been described with models that use stepwise cascades. Herein, we provide a novel perspective on the immunobiology of acute GVHD and briefly discuss some of the outstanding questions and limitations of the model systems.

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Section: Sensors Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

158

126

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“…Plasmacytoid regDCs might express CCR9 [26]; in cancer, plasmacytoid regDCs may be identified as cells expressing FOXO3 [27]. In addition, tumor-induced regDCs have been described as DCs expressing low levels of CD11c, MHC class II and co-stimulatory CD80 and CD86 molecules and high levels of CD11b [13,19].…”

Section: Characteristics Of Tumor-induced Regulatory Dendritic Cellsmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Shurin

2013

Cancer Microenvironment

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Three major functional subsets of dendritic cells (DCs) have been described in the tumor microenvironment in patients with cancer and tumor-bearing animals: (i) conventional DCs with intact antigen-presenting capabilities, (ii) functionally defective DCs with decreased motility and low ability to uptake, process and present antigens or produce cytokines and (iii) regulatory DCs with high capacity to suppress T cell proliferation, induce differentiation of regulatory T cells or support immune tolerance. Phenotypic characteristics of regulatory DCs (regDCs), as well as the mechanisms of T cell inhibition, vary in different experimental conditions and environments, suggesting high level of their plasticity and probably different origin. Although new data demonstrate that regDCs may play an important role at early stages of tumor development, functional differences and clinical significance of emergence of different myeloid regulatory cells (MDSCs, regDCs, M2 macrophages, N2 neutrophils, mast cells) in cancer remain to be determined.

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“…PDCs have also been demonstrated to cross-present viral Ags derived from infected cells or directly from viral particles to CD8 + T cells in vitro (24)(25)(26), although it is still controversial if this also occurs in vivo (20). The data that are available to date show that Ag presentation by PDCs can induce both T cell-mediated tolerance (27)(28)(29)(30) and immunity (18,(23)(24)(25)(26). The outcome of Ag delivery to PDCs in vivo with regard to the type of T cell response that is induced is therefore not predictable and is likely to depend on the route of Ag delivery and the mode of stimulation.…”

mentioning

confidence: 99%

Antigen Delivery to Plasmacytoid Dendritic Cells via BST2 Induces Protective T Cell-Mediated Immunity

Loschko

Schlitzer

Dudziak

et al. 2011

The Journal of Immunology

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Plasmacytoid dendritic cells (PDCs) are capable of presenting Ags to T cells in a tolerogenic or immunogenic manner depending on the formulation of the Ag and the mode of stimulation. It has not been investigated whether effective adaptive immune responses useful for vaccination can be induced by Ab-mediated Ag targeting to PDCs in vivo. In this study, we show that Ag delivered to murine PDCs via bone marrow stromal cell Ag 2 (BST2)/CD317 in combination with TLR agonists as adjuvants is specifically presented by PDCs in vivo and elicits strong cellular and humoral immune responses. These include IFN-γ production by CD4+ T cells and high Ab titers with a broad range of IgG isotypes. In addition, BST2-mediated Ag delivery in the presence of polyinosinic-polycytidylic acid as adjuvant induces cytotoxic T lymphocytes that are functional in vivo. A single immunization with Ag-fused anti-BST2 Ab together with polyinosinic-polycytidylic acid as adjuvant is sufficient to trigger protective immunity against subsequent viral infection and tumor growth. We conclude that despite the potential tolerogenic properties of PDCs, Ag targeting to PDCs in combination with TLR agonists as adjuvants is an effective vaccination strategy.

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CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease

Cited by 274 publications

References 55 publications

New perspectives on the biology of acute GVHD

New perspectives on the biology of acute GVHD

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Antigen Delivery to Plasmacytoid Dendritic Cells via BST2 Induces Protective T Cell-Mediated Immunity

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