Decisions About Dendritic Cells: Past, Present, and Future

Steinman, Ralph M.

doi:10.1146/annurev-immunol-100311-102839

Cited by 1,069 publications

(904 citation statements)

References 132 publications

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“…In mice, circulating monocytes can give rise to inflammatory DCs in vivo but whether the same holds true for humans remains unclear [57]. The observation that human monocytes can readily be differentiated into monocyte-derived DCs in the presence of GM-CSF and IL-4 in vitro [58] fundamentally transformed our understanding of DC-driven immune responses and facilitated investigations into many aspects of human DC biology including their potential as cellular vaccines [59]. Yet, the physiological relevance of these monocyte-derived DCs and the processes that drive monocyte differentiation into professional APCs in vivo are still only poorly understood.…”

Section: Differentiation Of Monocytes: Local Generation Of Inflammatomentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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Section: Differentiation Of Monocytes: Local Generation Of Inflammatomentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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“…1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression.…”

Section: Open Questionsmentioning

confidence: 99%

“…[10][11][12][13] Two major subsets of cDCs have been identified: cluster of differentiation 8a þ (CD8a þ ) cDCs and CD11b þ cDCs. 1,2,4,14 CD8a þ cDCs efficiently present exogenous antigens to CD8 þ T cells; these cells also require Id2 and basic leucine zipper transcription factor, ATF-like 3 (Batf3) for their differentiation, 15,16 but a Batf3-independent pathway has also been described for their generation. 17 CD11b þ cDCs preferentially activate CD4 þ T cells and require Kruppel-like factor 4 for their differentiation.…”

Section: Classes Of Dcsmentioning

confidence: 99%

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

2014

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Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis. Cell Death and Differentiation (2015) 22, 215-224; doi:10.1038/cdd.2014; published online 29 August 2014 FactsDendritic cells (DCs) control central and peripheral tolerance through their effects on effector and regulatory T cells. Specific signaling pathways regulate the ability of different DC populations to promote effector and regulatory T-cell responses. Abnormalities in DC numbers, recruitment and function contribute to the pathology of multiple sclerosis (MS) and can be partially overcome by the use of disease-modifying therapies and the targeting of specific molecular pathways. Nanotechnology provides new tools for the modulation of DC activity in vivo and the therapeutic induction of antigenspecific tolerance in immune-mediated disorders. Open QuestionsAlthough DC populations that promote the development of forkhead box P3-positive (FoxP3 þ ) regulatory T cells (Tregs) have been identified, it is not yet clear whether these populations constitute separate tolerogenic DC lineages or represent alternative activation or maturation states of other DC populations. What are the different molecular pathways that control the DC's ability to prime effector or tolerogenic T-cell responses?There is an unmet clinical need for the development of methods for the efficient and consistent generation of tolerogenic DCs in vitro and in vivo that can be implemented in large-scale clinical setups.Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that control the activation and polarization of T cells into specific lineages and, consequently, the generation of antigen-specific antibody and T-cell responses. 1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression. Thus, DCs have a central role in the control of the adaptive immune response to pathogens and selftissues and therefore constitute potential targets for the therapeutic modulation of the immune response. In this review, we discus the role of DCs in autoimmune diseases, with a special emphasis on their role in the modulation of central nervous system (CNS) inflammation in MS. Received 12.6.14; accepted 23.6.14; Edited by H-U Simon; published online 29.8.14 Abbreviations: A...

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“…8 Example of a figure with the title tag included in the figures and not in the caption. Source: [51] and additional explanations should be added in the legend for the nomenclature, abbreviations, arrows, symbols, letters, and units used in a figure. Two guidelines offer advice on legends about images presenting specific data types, such as pooled data, schemes, and structural chemical formulas.…”

Section: Image Title and Legendmentioning

confidence: 99%

“…11 Example of an image menu and image preview on the same page as the article. Source: [51] Fig . 12 Example of an image menu on the same page as the article.…”

Section: Sciencementioning

confidence: 99%

Do Physicians Make Their Articles Readable for Their Blind or Low-Vision Patients? An Analysis of Current Image Processing Practices in Biomedical Journals from the Point of View of Accessibility

et al. 2014

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Visual content in biomedical academic papers is a growing source of critical information, but it is not always fully readable for people with visual impairments. We aimed to assess current image processing practices, accessibility policies, and submission policies in a sample of 12 highly cited biomedical journals. We manually checked the application of text-based alternative image descriptions for every image in 12 articles (one for each journal). We determined whether the journals claimed to follow an accessibility policy and we reviewed their submission policy and their guidelines related to the visual content. We identified important features concerning the processing of images and the characteristics of the visual and the retrieval options of visual content offered by the publishers. The evaluation shows that the actual practices of textual image description in highly cited biomedical journals do not follow general guidelines on accessibility. The images within the articles analyzed lack alternative descriptions or have uninformative descriptions, even in the case of journals claiming to follow an accessibility policy. Consequently, the visual information of scientific articles is not accessible to people with severe visual disabilities.Instructions on image submission are heterogeneous and a declaration of accessibility guidelines was only found in two thirds of the sample of journals, with one third not explicitly following any accessibility policy, although they are required to by law.

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Decisions About Dendritic Cells: Past, Present, and Future

Cited by 1,069 publications

References 132 publications

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

Do Physicians Make Their Articles Readable for Their Blind or Low-Vision Patients? An Analysis of Current Image Processing Practices in Biomedical Journals from the Point of View of Accessibility

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