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  • Microglia and macrophages in brain homeostasis and disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-20
    Qingyun Li, Ben A. Barres

    Microglia and macrophages in brain homeostasis and disease Microglia and macrophages in brain homeostasis and disease, Published online: 20 November 2017; doi:10.1038/nri.2017.125 This Review describes recent advances in our understanding of the ontogeny, development and function of brain-resident macrophages and microglia, including their normal functions during brain development and homeostasis and how disturbance of these functions may precipitate neurodegenerative and neuropsychiatric diseases.

    更新日期:2017-11-20
  • Microglia and macrophages in brain homeostasis and disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-20
    Qingyun Li, Ben A. Barres

    Microglia and macrophages in brain homeostasis and disease Microglia and macrophages in brain homeostasis and disease, Published online: 20 November 2017; doi:10.1038/nri.2017.125 This Review describes recent advances in our understanding of the ontogeny, development and function of brain-resident macrophages and microglia, including their normal functions during brain development and homeostasis and how disturbance of these functions may precipitate neurodegenerative and neuropsychiatric diseases.

    更新日期:2017-11-20
  • MHC molecules: Immune editing shapes the cancer landscape
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-13
    Shimona Starling

    MHC molecules: Immune editing shapes the cancer landscape MHC molecules: Immune editing shapes the cancer landscape, Published online: 13 November 2017; doi:10.1038/nri.2017.129 NatureArticleSnippet(type=short-summary, markup= HLA variation or loss is associated with immune editing in human tumours. , isJats=true)

    更新日期:2017-11-13
  • Dendritic cells: Managing migration
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-13
    Kirsty Minton

    Dendritic cells: Managing migration Dendritic cells: Managing migration, Published online: 13 November 2017; doi:10.1038/nri.2017.128 NatureArticleSnippet(type=short-summary, markup= Lysosomal calcium signalling links antigen uptake by tissue dendritic cells to migration to the lymph nodes. , isJats=true)

    更新日期:2017-11-13
  • MHC molecules: Immune editing shapes the cancer landscape
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-13
    Shimona Starling

    MHC molecules: Immune editing shapes the cancer landscape MHC molecules: Immune editing shapes the cancer landscape, Published online: 13 November 2017; doi:10.1038/nri.2017.129 NatureArticleSnippet(type=short-summary, markup= HLA variation or loss is associated with immune editing in human tumours. , isJats=true)

    更新日期:2017-11-13
  • Dendritic cells: Managing migration
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-13
    Kirsty Minton

    Dendritic cells: Managing migration Dendritic cells: Managing migration, Published online: 13 November 2017; doi:10.1038/nri.2017.128 NatureArticleSnippet(type=short-summary, markup= Lysosomal calcium signalling links antigen uptake by tissue dendritic cells to migration to the lymph nodes. , isJats=true)

    更新日期:2017-11-13
  • Immunometabolism: T cells activate the fear
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-07
    Shimona Starling

    Immunometabolism: T cells activate the fearImmunometabolism: T cells activate the fear, Published online: 07 November 2017; doi:10.1038/nri.2017.126NatureArticleSnippet(type=short-summary, markup=T cell activation is associated with a depletion of amino acids and neurotransmitters and may result in behavioural changes, isJats=true)

    更新日期:2017-11-07
  • How poverty affects diet to shape the microbiota and chronic disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-07
    Christy A. Harrison, Douglas Taren

    Here, we discuss the link between nutrition, non-communicable chronic diseases and socio-economic standing, with a special focus on the microbiota. We provide a theoretical framework and several lines of evidence from both animal and human studies that support the idea that income inequality is an underlying factor for the maladaptive changes seen in the microbiota in certain populations. We propose that this contributes to the health disparities that are seen between lower-income and higher-income populations in high-income countries.

    更新日期:2017-11-07
  • Inflammation: Inflammatory memory is skin deep
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-07
    Yvonne Bordon

    Inflammation: Inflammatory memory is skin deepInflammation: Inflammatory memory is skin deep, Published online: 07 November 2017; doi:10.1038/nri.2017.127NatureArticleSnippet(type=short-summary, markup=Skin epithelial stem cells show inflammatory memory, which enhances their response to tissue damage., isJats=true)

    更新日期:2017-11-07
  • Immunometabolism: T cells activate the fear
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-07
    Shimona Starling

    Immunometabolism: T cells activate the fearImmunometabolism: T cells activate the fear, Published online: 07 November 2017; doi:10.1038/nri.2017.126NatureArticleSnippet(type=short-summary, markup=T cell activation is associated with a depletion of amino acids and neurotransmitters and may result in behavioural changes, isJats=true)

    更新日期:2017-11-07
  • How poverty affects diet to shape the microbiota and chronic disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-07
    Christy A. Harrison, Douglas Taren

    Here, we discuss the link between nutrition, non-communicable chronic diseases and socio-economic standing, with a special focus on the microbiota. We provide a theoretical framework and several lines of evidence from both animal and human studies that support the idea that income inequality is an underlying factor for the maladaptive changes seen in the microbiota in certain populations. We propose that this contributes to the health disparities that are seen between lower-income and higher-income populations in high-income countries.

    更新日期:2017-11-07
  • Inflammation: Inflammatory memory is skin deep
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-07
    Yvonne Bordon

    Inflammation: Inflammatory memory is skin deepInflammation: Inflammatory memory is skin deep, Published online: 07 November 2017; doi:10.1038/nri.2017.127NatureArticleSnippet(type=short-summary, markup=Skin epithelial stem cells show inflammatory memory, which enhances their response to tissue damage., isJats=true)

    更新日期:2017-11-07
  • TH2 cell development and function
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-10-30
    Jennifer A. Walker, Andrew N. J. McKenzie

    T helper 2 (TH2) cells orchestrate protective type 2 immune responses, such as those that target helminths and facilitate tissue repair, but also contribute to chronic inflammatory diseases, such as asthma and allergy. Here, we review recent insights into how diverse molecular signals from cellular sources, including dendritic cells, innate lymphoid cells and the epithelium, are integrated by T cells to guide the transcriptional and epigenetic changes necessary for TH2 cell differentiation. Our improved understanding of these pathways has opened new avenues for therapeutically targeting TH2 cells in asthma and allergy. The advent of comprehensive single-cell transcriptomics along with improvements in single-cell proteomics and the generation of novel in vivo cell fate mapping techniques promise to expand our understanding of T cell diversity and offer new insight into disease-related heterogeneity and plasticity of TH cell responses.

    更新日期:2017-10-30
  • New beginnings
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-10-30
    Florent Ginhoux

    New beginnings Nature Reviews Immunology, Published online: 30 October 2017; doi:10.1038/nri.2017.91 Florent Ginhoux reflects on a 2002 paper by Merad and colleagues that challenged the dogma that adult Langerhans cells arise from blood-circulating precursors.

    更新日期:2017-10-30
  • Neutrophils: Neutrophil differentiation is autophagy dependent
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-01
    Peter Sidaway

    Neutrophils: Neutrophil differentiation is autophagy dependent Nature Reviews Immunology, Published online: 27 October 2017; doi:10.1038/nri.2017.122 Metabolism of free fatty acids by cell-intrinsic autophagy is an essential component of neutrophil differentiation.

    更新日期:2017-10-30
  • Innate immunity: Fibrinolytic and innate systems collide
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-01
    Mina Razzak

    Innate immunity: Fibrinolytic and innate systems collide Nature Reviews Immunology, Published online: 27 October 2017; doi:10.1038/nri.2017.124 Nuclear factor of activated T cells (NFAT) regulates IFNγ production in natural killer cells and controls fibrinolytic processes required to clear skin infections.

    更新日期:2017-10-30
  • Regulatory T Cells: The IL-2 gauge
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-01
    Lucy Bird

    Regulatory T Cells: The IL-2 gauge Nature Reviews Immunology, Published online: 27 October 2017; doi:10.1038/nri.2017.123 T follicular regulatory cells arise once infection resolves and IL-2 levels wane to prevent the outgrowth of self-reactive B cells.

    更新日期:2017-10-30
  • Beyond binding: antibody effector functions in infectious diseases
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-10-24
    Lenette L. Lu, Todd J. Suscovich, Sarah M. Fortune, Galit Alter

    Antibodies play an essential role in host defence against pathogens by recognizing microorganisms or infected cells. Although preventing pathogen entry is one potential mechanism of protection, antibodies can control and eradicate infections through a variety of other mechanisms. In addition to binding and directly neutralizing pathogens, antibodies drive the clearance of bacteria, viruses, fungi and parasites via their interaction with the innate and adaptive immune systems, leveraging a remarkable diversity of antimicrobial processes locked within our immune system. Specifically, antibodies collaboratively form immune complexes that drive sequestration and uptake of pathogens, clear toxins, eliminate infected cells, increase antigen presentation and regulate inflammation. The diverse effector functions that are deployed by antibodies are dynamically regulated via differential modification of the antibody constant domain, which provides specific instructions to the immune system. Here, we review mechanisms by which antibody effector functions contribute to the balance between microbial clearance and pathology and discuss tractable lessons that may guide rational vaccine and therapeutic design to target gaps in our infectious disease armamentarium.

    更新日期:2017-10-30
  • TH2 cell development and function
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-10-30
    Jennifer A. Walker, Andrew N. J. McKenzie

    T helper 2 (TH2) cells orchestrate protective type 2 immune responses, such as those that target helminths and facilitate tissue repair, but also contribute to chronic inflammatory diseases, such as asthma and allergy. Here, we review recent insights into how diverse molecular signals from cellular sources, including dendritic cells, innate lymphoid cells and the epithelium, are integrated by T cells to guide the transcriptional and epigenetic changes necessary for TH2 cell differentiation. Our improved understanding of these pathways has opened new avenues for therapeutically targeting TH2 cells in asthma and allergy. The advent of comprehensive single-cell transcriptomics along with improvements in single-cell proteomics and the generation of novel in vivo cell fate mapping techniques promise to expand our understanding of T cell diversity and offer new insight into disease-related heterogeneity and plasticity of TH cell responses.

    更新日期:2017-10-30
  • New beginnings
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-10-30
    Florent Ginhoux

    New beginnings Nature Reviews Immunology, Published online: 30 October 2017; doi:10.1038/nri.2017.91 Florent Ginhoux reflects on a 2002 paper by Merad and colleagues that challenged the dogma that adult Langerhans cells arise from blood-circulating precursors.

    更新日期:2017-10-30
  • Neutrophils: Neutrophil differentiation is autophagy dependent
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-01
    Peter Sidaway

    Neutrophils: Neutrophil differentiation is autophagy dependent Nature Reviews Immunology, Published online: 27 October 2017; doi:10.1038/nri.2017.122 Metabolism of free fatty acids by cell-intrinsic autophagy is an essential component of neutrophil differentiation.

    更新日期:2017-10-30
  • Innate immunity: Fibrinolytic and innate systems collide
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-01
    Mina Razzak

    Innate immunity: Fibrinolytic and innate systems collide Nature Reviews Immunology, Published online: 27 October 2017; doi:10.1038/nri.2017.124 Nuclear factor of activated T cells (NFAT) regulates IFNγ production in natural killer cells and controls fibrinolytic processes required to clear skin infections.

    更新日期:2017-10-30
  • Regulatory T Cells: The IL-2 gauge
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-11-01
    Lucy Bird

    Regulatory T Cells: The IL-2 gauge Nature Reviews Immunology, Published online: 27 October 2017; doi:10.1038/nri.2017.123 T follicular regulatory cells arise once infection resolves and IL-2 levels wane to prevent the outgrowth of self-reactive B cells.

    更新日期:2017-10-30
  • Beyond binding: antibody effector functions in infectious diseases
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-10-24
    Lenette L. Lu, Todd J. Suscovich, Sarah M. Fortune, Galit Alter

    Beyond binding: antibody effector functions in infectious diseases Nature Reviews Immunology, Published online: 24 October 2017; doi:10.1038/nri.2017.106 Antibodies play an essential role in host defence against pathogens by binding to microorganisms and infected cells and exerting various effector functions. In this Review, Lu and colleagues summarize antibody isotypes and subclasses, modifications, receptor binding and signalling and effector functions in the context of infectious diseases.

    更新日期:2017-10-30
  • Immune tolerance: A mother's greatest gift is TIM3
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Shimona Starling

    Immune tolerance: A mother's greatest gift is TIM3 Nature Reviews Immunology, Published online: 16 October 2017; doi:10.1038/nri.2017.120 Maternal–fetal tolerance is promoted by TIM3 signalling in peripheral natural killer cells.

    更新日期:2017-10-16
  • The hygiene hypothesis in autoimmunity: the role of pathogens and commensals
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jean-François Bach

    The incidence of autoimmune diseases has been steadily rising. Concomitantly, the incidence of most infectious diseases has declined. This observation gave rise to the hygiene hypothesis, which postulates that a reduction in the frequency of infections contributes directly to the increase in the frequency of autoimmune and allergic diseases. This hypothesis is supported by robust epidemiological data, but the underlying mechanisms are unclear. Pathogens are known to be important, as autoimmune disease is prevented in various experimental models by infection with different bacteria, viruses and parasites. Gut commensal bacteria also play an important role: dysbiosis of the gut flora is observed in patients with autoimmune diseases, although the causal relationship with the occurrence of autoimmune diseases has not been established. Both pathogens and commensals act by stimulating immunoregulatory pathways. Here, I discuss the importance of innate immune receptors, in particular Toll-like receptors, in mediating the protective effect of pathogens and commensals on autoimmunity.

    更新日期:2017-10-16
  • Neuroimmunology: ILC2s touch a nerve
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Yvonne Bordon

    Neuroimmunology: ILC2s touch a nerve Nature Reviews Immunology, Published online: 16 October 2017; doi:10.1038/nri.2017.119 Mucosal neurons activate ILC2s and drive type 2 inflammation by secreting neuromedin U.

    更新日期:2017-10-16
  • Immune tolerance: A mother's greatest gift is TIM3
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Shimona Starling

    Immune tolerance: A mother's greatest gift is TIM3 Nature Reviews Immunology, Published online: 16 October 2017; doi:10.1038/nri.2017.120 Maternal–fetal tolerance is promoted by TIM3 signalling in peripheral natural killer cells.

    更新日期:2017-10-16
  • The hygiene hypothesis in autoimmunity: the role of pathogens and commensals
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jean-François Bach

    The incidence of autoimmune diseases has been steadily rising. Concomitantly, the incidence of most infectious diseases has declined. This observation gave rise to the hygiene hypothesis, which postulates that a reduction in the frequency of infections contributes directly to the increase in the frequency of autoimmune and allergic diseases. This hypothesis is supported by robust epidemiological data, but the underlying mechanisms are unclear. Pathogens are known to be important, as autoimmune disease is prevented in various experimental models by infection with different bacteria, viruses and parasites. Gut commensal bacteria also play an important role: dysbiosis of the gut flora is observed in patients with autoimmune diseases, although the causal relationship with the occurrence of autoimmune diseases has not been established. Both pathogens and commensals act by stimulating immunoregulatory pathways. Here, I discuss the importance of innate immune receptors, in particular Toll-like receptors, in mediating the protective effect of pathogens and commensals on autoimmunity.

    更新日期:2017-10-16
  • Neuroimmunology: ILC2s touch a nerve
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Yvonne Bordon

    Neuroimmunology: ILC2s touch a nerve Nature Reviews Immunology, Published online: 16 October 2017; doi:10.1038/nri.2017.119 Mucosal neurons activate ILC2s and drive type 2 inflammation by secreting neuromedin U.

    更新日期:2017-10-16
  • The diverse functions of the PD1 inhibitory pathway
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Arlene H. Sharpe, Kristen E. Pauken

    T cell activation is a highly regulated process involving peptide–MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.

    更新日期:2017-10-11
  • Immune checkpoint blockade in infectious diseases
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Michelle N. Wykes, Sharon R. Lewin

    The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting.

    更新日期:2017-10-11
  • Neutrophil extracellular traps in immunity and disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Venizelos Papayannopoulos

    Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer. Here, I discuss the key findings and concepts that have thus far shaped the field of NET biology.

    更新日期:2017-10-11
  • Regulation of immunity and inflammation by hypoxia in immunological niches
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Cormac T. Taylor, Sean P. Colgan

    Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

    更新日期:2017-10-11
  • Breastfeeding-related maternal microchimerism
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jean-Pierre Molès, Edouard Tuaillon, Chipepo Kankasa, Anne-Sophie Bedin, Nicolas Nagot, Arnaud Marchant, Joann M. McDermid, Philippe Van de Perre

    Breastfeeding-related maternal microchimerism Nature Reviews Immunology, Published online: 3 October 2017; doi:10.1038/nri.2017.115

    更新日期:2017-10-11
  • Reply: Breastfeeding-related maternal microchimerism
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jeremy M. Kinder, Ina A. Stelzer, Petra C. Arck, Sing Sing Way

    Reply: Breastfeeding-related maternal microchimerism Nature Reviews Immunology, Published online: 3 October 2017; doi:10.1038/nri.2017.117

    更新日期:2017-10-11
  • The diverse functions of the PD1 inhibitory pathway
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Arlene H. Sharpe, Kristen E. Pauken

    T cell activation is a highly regulated process involving peptide–MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.

    更新日期:2017-10-11
  • Immune checkpoint blockade in infectious diseases
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Michelle N. Wykes, Sharon R. Lewin

    The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting.

    更新日期:2017-10-11
  • Neutrophil extracellular traps in immunity and disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Venizelos Papayannopoulos

    Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer. Here, I discuss the key findings and concepts that have thus far shaped the field of NET biology.

    更新日期:2017-10-11
  • Regulation of immunity and inflammation by hypoxia in immunological niches
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Cormac T. Taylor, Sean P. Colgan

    Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

    更新日期:2017-10-11
  • Breastfeeding-related maternal microchimerism
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jean-Pierre Molès, Edouard Tuaillon, Chipepo Kankasa, Anne-Sophie Bedin, Nicolas Nagot, Arnaud Marchant, Joann M. McDermid, Philippe Van de Perre

    Breastfeeding-related maternal microchimerism Nature Reviews Immunology, Published online: 3 October 2017; doi:10.1038/nri.2017.115

    更新日期:2017-10-11
  • Reply: Breastfeeding-related maternal microchimerism
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jeremy M. Kinder, Ina A. Stelzer, Petra C. Arck, Sing Sing Way

    Reply: Breastfeeding-related maternal microchimerism Nature Reviews Immunology, Published online: 3 October 2017; doi:10.1038/nri.2017.117

    更新日期:2017-10-11
  • The spectrum of T cell metabolism in health and disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Glenn R. Bantug, Lorenzo Galluzzi, Guido Kroemer, Christoph Hess

    In healthy individuals, metabolically quiescent T cells survey lymph nodes and peripheral tissues in search of cognate antigens. During infection, T cells that encounter cognate antigens are activated and — in a context-specific manner — proliferate and/or differentiate to become effector T cells. This process is accompanied by important changes in cellular metabolism (known as metabolic reprogramming). The magnitude and spectrum of metabolic reprogramming as it occurs in T cells in the context of acute infection ensure host survival. By contrast, altered T cell metabolism, and hence function, is also observed in various disease states, in which T cells actively contribute to pathology. In this Review, we introduce the idea that the spectrum of immune cell metabolic states can provide a basis for categorizing human diseases. Specifically, we first summarize the metabolic and interlinked signalling requirements of T cells responding to acute infection. We then discuss how metabolic reprogramming of T cells is linked to disease.

    更新日期:2017-09-25
  • The spectrum of T cell metabolism in health and disease
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Glenn R. Bantug, Lorenzo Galluzzi, Guido Kroemer, Christoph Hess

    In healthy individuals, metabolically quiescent T cells survey lymph nodes and peripheral tissues in search of cognate antigens. During infection, T cells that encounter cognate antigens are activated and — in a context-specific manner — proliferate and/or differentiate to become effector T cells. This process is accompanied by important changes in cellular metabolism (known as metabolic reprogramming). The magnitude and spectrum of metabolic reprogramming as it occurs in T cells in the context of acute infection ensure host survival. By contrast, altered T cell metabolism, and hence function, is also observed in various disease states, in which T cells actively contribute to pathology. In this Review, we introduce the idea that the spectrum of immune cell metabolic states can provide a basis for categorizing human diseases. Specifically, we first summarize the metabolic and interlinked signalling requirements of T cells responding to acute infection. We then discuss how metabolic reprogramming of T cells is linked to disease.

    更新日期:2017-09-25
  • Neuroimmunology: JAK in the itch
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Yvonne Bordon

    Neuroimmunology: JAK in the itch Nature Reviews Immunology, Published online: 18 September 2017; doi:10.1038/nri.2017.114 Chronic itch is driven by IL-4 receptor- and JAK1-mediated signalling in sensory neurons.

    更新日期:2017-09-20
  • γδ T cells in homeostasis and host defence of epithelial barrier tissues
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Morten M. Nielsen, Deborah A. Witherden, Wendy L. Havran

    Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body — namely, the epidermis and the intestine — and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we describe epithelium-specific butyrophilin-like molecules and briefly review their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires.

    更新日期:2017-09-20
  • Neutrophils: Interfering with intestinal inflammation
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Shimona Starling

    Neutrophils: Interfering with intestinal inflammation Nature Reviews Immunology, Published online: 18 September 2017; doi:10.1038/nri.2017.113 IFNλ can modulate the function of neutrophils and suppress intestinal inflammation.

    更新日期:2017-09-20
  • Complement in cancer: untangling an intricate relationship
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Edimara S. Reis, Dimitrios C. Mastellos, Daniel Ricklin, Alberto Mantovani, John D. Lambris

    In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis. It also offers insight into clinical aspects, including the feasibility of using complement biomarkers for cancer diagnosis and the use of complement inhibitors during cancer treatment.

    更新日期:2017-09-20
  • Neutrophils: Interfering with intestinal inflammation
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Shimona Starling

    IFNλ can modulate the function of neutrophils and suppress intestinal inflammation.

    更新日期:2017-09-19
  • γδ T cells in homeostasis and host defence of epithelial barrier tissues
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Morten M. Nielsen, Deborah A. Witherden, Wendy L. Havran

    Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body — namely, the epidermis and the intestine — and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we describe epithelium-specific butyrophilin-like molecules and briefly review their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires.

    更新日期:2017-09-19
  • Neuroimmunology: JAK in the itch
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Yvonne Bordon

    Chronic itch is driven by IL-4 receptor- and JAK1-mediated signalling in sensory neurons.

    更新日期:2017-09-19
  • Complement in cancer: untangling an intricate relationship
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Edimara S. Reis, Dimitrios C. Mastellos, Daniel Ricklin, Alberto Mantovani, John D. Lambris

    In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis. It also offers insight into clinical aspects, including the feasibility of using complement biomarkers for cancer diagnosis and the use of complement inhibitors during cancer treatment.

    更新日期:2017-09-19
  • Mucosal immunology: Probiotic induction of tolerogenic T cells in the gut
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Katharine H. Wrighton

    Mucosal immunology: Probiotic induction of tolerogenic T cells in the gut Nature Reviews Immunology, Published online: 11 September 2017; doi:10.1038/nri.2017.110 A probiotic induces CD4+ T cell differentiation into tolerogenic double-positive intraepithelial lymphocytes by activating their aryl hydrocarbon receptor.

    更新日期:2017-09-16
  • Immune homeostasis: Regulatory ILCs don't rely on FOXP3
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Yvonne Bordon

    Immune homeostasis: Regulatory ILCs don't rely on FOXP3 Nature Reviews Immunology, Published online: 11 September 2017; doi:10.1038/nri.2017.107 The identification of a regulatory innate lymphoid cell subset in the intestine.

    更新日期:2017-09-16
  • T cells: Proteasome dictates CD8+ T cell fate
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Shimona Starling

    T cells: Proteasome dictates CD8+ T cell fate Nature Reviews Immunology, Published online: 11 September 2017; doi:10.1038/nri.2017.109 Endogenous proteasome activity can modulate the fate and function of CD8+ T cells.

    更新日期:2017-09-16
  • Functions of tissue-resident eosinophils
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Peter F. Weller, Lisa A. Spencer

    Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, 'non-effector' functions in health and disease.

    更新日期:2017-09-16
  • Organ-specific protection mediated by cooperation between vascular and epithelial barriers
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Ilaria Spadoni, Giulia Fornasa, Maria Rescigno

    Immune privilege is a complex process that protects organs from immune-mediated attack and damage. It is accomplished by a series of cellular barriers that both control immune cell entry and promote the development of tolerogenic immune cells. In this Review, we describe the vascular endothelial and epithelial barriers in organs that are commonly considered to be immune privileged, such as the brain and the eye. We compare these classical barriers with barriers in the intestine, which share features with barriers of immune-privileged organs, such as the capacity to induce tolerance and to protect from external insults. We suggest that when intestinal barriers break down, disruption of other barriers at distant sites can ensue, and this may underlie the development of various neurological, metabolic and intestinal disorders.

    更新日期:2017-09-16
  • Tumour immunology: Cell cycle inhibitors boost tumour immunogenicity
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 2017-08-30
    Kirsty Minton

    Tumour immunology: Cell cycle inhibitors boost tumour immunogenicity Nature Reviews Immunology, Published online: 30 August 2017; doi:10.1038/nri.2017.104 Cyclin-dependent kinase inhibitors promote tumour regression by increasing antigen presentation and decreasing immune regulation.

    更新日期:2017-09-16
  • Type 2 immunity in tissue repair and fibrosis
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Richard L. Gieseck III, Mark S. Wilson, Thomas A. Wynn

    Type 2 immunity is characterized by the production of IL-4, IL-5, IL-9 and IL-13, and this immune response is commonly observed in tissues during allergic inflammation or infection with helminth parasites. However, many of the key cell types associated with type 2 immune responses — including T helper 2 cells, eosinophils, mast cells, basophils, type 2 innate lymphoid cells and IL-4- and IL-13-activated macrophages — also regulate tissue repair following injury. Indeed, these cell populations engage in crucial protective activity by reducing tissue inflammation and activating important tissue-regenerative mechanisms. Nevertheless, when type 2 cytokine-mediated repair processes become chronic, over-exuberant or dysregulated, they can also contribute to the development of pathological fibrosis in many different organ systems. In this Review, we discuss the mechanisms by which type 2 immunity contributes to tissue regeneration and fibrosis following injury.

    更新日期:2017-09-16
  • Synthetic immune niches for cancer immunotherapy
    Nat. Rev. Immunol. (IF 39.932) Pub Date : 
    Jorieke Weiden, Jurjen Tel, Carl G. Figdor

    Synthetic immune niches for cancer immunotherapy Nature Reviews Immunology, Published online: 30 August 2017; doi:10.1038/nri.2017.89 Carl Figdor and colleagues propose that delivering cancer immunotherapy in the context of engineered three-dimensional scaffolds may boost anticancer immunity. The synthetic scaffolds, which can be linked to immunomodulatory factors, can act as immune niches to support the priming and maintenance of antitumour immune responses.

    更新日期:2017-09-16
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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