Author
Nobuyuki Onai
Other affiliations: University of Tokyo, University of California, Los Angeles, Tokyo Medical and Dental University ...read more
Bio: Nobuyuki Onai is an academic researcher from Kanazawa Medical University. The author has contributed to research in topics: Dendritic cell & Progenitor cell. The author has an hindex of 31, co-authored 57 publications receiving 5976 citations. Previous affiliations of Nobuyuki Onai include University of Tokyo & University of California, Los Angeles.
Papers published on a yearly basis
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TL;DR: This Opinion article suggests that the mononuclear phagocyte system can be classified primarily by their ontogeny and secondarily by their location, function and phenotype, which permits a more robust classification during both steady-state and inflammatory conditions.
Abstract: The mononuclear phagocyte system (MPS) has historically been categorized into monocytes, dendritic cells and macrophages on the basis of functional and phenotypical characteristics. However, considering that these characteristics are often overlapping, the distinction between and classification of these cell types has been challenging. In this Opinion article, we propose a unified nomenclature for the MPS. We suggest that these cells can be classified primarily by their ontogeny and secondarily by their location, function and phenotype. We believe that this system permits a more robust classification during both steady-state and inflammatory conditions, with the benefit of spanning different tissues and across species.
1,404 citations
TL;DR: This work identifies highly cycling Lin−c-KitintFlt3+M-CSFR+ cells with a distinct gene-expression profile in mouse bone marrow that efficiently generated plasmacytoid and conventional DCs but no other lineages, which increased in number after in vivo injection of the cytokine Flt3 ligand.
Abstract: Lymphoid tissue plasmacytoid and conventional dendritic cells (DCs) are continuously regenerated from hematopoietic stem cells. The cytokine dependence and biology of plasmacytoid and conventional DCs suggest that regeneration might proceed through common DC-restricted developmental intermediates. By selecting for cytokine receptor expression relevant to DC development, we identify here highly cycling Lin(-)c-Kit(int)Flt3(+)M-CSFR(+) cells with a distinct gene-expression profile in mouse bone marrow that, on a clonal level in vitro and as a population both in vitro and in vivo, efficiently generated plasmacytoid and conventional DCs but no other lineages, which increased in number after in vivo injection of the cytokine Flt3 ligand. These clonogenic common DC progenitors thus define a cytokine-regulated DC developmental pathway that ensures the supply of various DC populations.
681 citations
TL;DR: In human B cells TLRs are downstream of BCR and play a role both in the primary response and in the memory phase, and the constitutive expression of TLRs in memory B cells allows polyclonal activation of the entire memory pool.
667 citations
TL;DR: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD.
Abstract: Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T H 2-type cells in lesional skin Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4–positive (CCR4 + ) or CCR8 + cells Objective: The purpose of this study was to investigate the participation of TARC in AD Methods: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors The positivity of CCR4 of CD4 + CD45RO + cells in PBMCs was examined by using FACS analysis Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD Results: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis The serum TARC levels significantly correlated with eosinophil number ( r = 061), SCORAD score ( r = 060), and serum soluble E-selectin levels ( r = 058) and weakly correlated with serum soluble IL-2 receptor levels ( r = 034) in patients with AD The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms The CCR4 positivity of CD4 + CD45RO + cells in PBMCs of patients with AD was also higher than that of healthy control subjects Immunohistochemical staining revealed that TARC was positive in ke-ratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis Conclusion: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD (J Allergy Clin Immunol 2001;107:535-41)
505 citations
TL;DR: It is shown that type I IFNs induce proliferation and exhaustion in hematopoietic stem cells (HSCs) and that interferon regulatory factor-2 (IRF2), a transcriptional suppressor of type IIFN signaling, preserves the self-renewal and multilineage differentiation capacity of HSCs.
Abstract: Type I interferons (IFNs), a family of cytokines, orchestrate numerous biological and cellular processes1, 2, 3. Although it is well known that type I IFNs are essential for establishing the host antiviral state4, their role in hematopoietic homeostasis has not been studied. Here we show that type I IFNs induce proliferation and exhaustion in hematopoietic stem cells (HSCs) and that interferon regulatory factor-2 (IRF2), a transcriptional suppressor of type I IFN signaling5, 6, preserves the self-renewal and multilineage differentiation capacity of HSCs. HSCs were substantially less abundant in the bone marrow of Irf2-/- as compared to Irf2+/- mice. Irf2-/- HSCs showed enhanced cell cycling status and failed to produce hematopoietic cells in competitive repopulation assays, and the reconstituting capacity of Irf2-/- HSCs was restored by disabling type I IFN signaling in these cells. In wild-type mice, injection of poly(I:C), an inducer of type I IFN signaling, or IFN- induced HSC proliferation, and chronic type I IFN signaling further reduced the number of quiescent HSCs. Notably, combined poly(I:C) and 5-fluorouracil (5-FU) treatment allowed exogenous HSC engraftment and hematopoietic reconstitution in WT mice. Our findings provide insight into the molecular basis for the maintenance of HSC quiescence and may lead to improvements in bone marrow transplantation and type I IFN-based therapies for viral infection and cancer.
385 citations
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TL;DR: Current understanding of the cellular and molecular mechanisms of fibrogenesis is explored and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs.
Abstract: Fibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen-producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial-mesenchymal (EMT/EndMT) transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen-associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL-13, IL-21, TGF-beta1), chemokines (MCP-1, MIP-1beta), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator-activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis.
3,390 citations
TL;DR: This work considers myeloid cells as an intricately connected, complex, single system and focuses on how tumours manipulate the myeloids system to evade the host immune response.
Abstract: Here, the authors discuss how the immune activities of myeloid cells, such as macrophages and dendritic cells, are affected by the immunosuppressive tumour environment. They propose that tumours can evade the immune system by promoting aberrant differentiation and function of the entire myeloid system.
2,966 citations
TL;DR: The current understanding of myeloid lineage development is reviewed and the developmental pathways and cues that drive differentiation are described, which are central to the development of immunologic memory and tolerance in mice.
Abstract: Monocytes and macrophages are critical effectors and regulators of inflammation and the innate immune response, the immediate arm of the immune system. Dendritic cells initiate and regulate the highly pathogen-specific adaptive immune responses and are central to the development of immunologic memory and tolerance. Recent in vivo experimental approaches in the mouse have unveiled new aspects of the developmental and lineage relationships among these cell populations. Despite this, the origin and differentiation cues for many tissue macrophages, monocytes, and dendritic cell subsets in mice, and the corresponding cell populations in humans, remain to be elucidated.
2,832 citations
TL;DR: Advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
Abstract: Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
2,372 citations
TL;DR: A fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression is reported, establishing that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly 6C(-) cells and that the abundance of Ly6 C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.
2,302 citations