LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 13

Search options

  1. Article ; Online: The Whole Body as the System in Systems Immunology

    Maya M.L. Poon / Donna L. Farber

    iScience, Vol 23, Iss 9, Pp 101509- (2020)

    2020  

    Abstract: Summary: The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue ... ...

    Abstract Summary: The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue homeostasis. Although much of our understanding of human immunology has derived from studies of peripheral blood, recent work utilizing human tissue resources and innovative computational methods have employed a whole-body, systems-based approach, revealing tremendous complexity and heterogeneity of the immune system within individuals and across the population. In this review, we discuss how tissue localization, developmental and age-associated changes, and conditions of health and disease shape the immune response, as well as how improved understanding of interindividual and tissue-specific immunity can be leveraged for developing targeted therapeutics.
    Keywords Immunology ; Complex System Biology ; Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Dissecting lung development and fibrosis at single-cell resolution

    Donna L. Farber / Peter A. Sims

    Genome Medicine, Vol 11, Iss 1, Pp 1-

    2019  Volume 3

    Abstract: Editorial summary Single-cell transcriptome profiling has enabled high-resolution analysis of cellular populations in tissues during development, health, and disease. Recent studies make innovative use of single-cell RNA sequencing (scRNAseq) to ... ...

    Abstract Editorial summary Single-cell transcriptome profiling has enabled high-resolution analysis of cellular populations in tissues during development, health, and disease. Recent studies make innovative use of single-cell RNA sequencing (scRNAseq) to investigate mechanisms that allow immune cells to interact with tissue components in the lung during development and fibrotic lung disease.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Maintenance of the human memory T cell repertoire by subset and tissue site

    Michelle Miron / Wenzhao Meng / Aaron M. Rosenfeld / Shirit Dvorkin / Maya Meimei Li Poon / Nora Lam / Brahma V. Kumar / Yoram Louzoun / Eline T. Luning Prak / Donna L. Farber

    Genome Medicine, Vol 13, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Abstract Background Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating ...

    Abstract Abstract Background Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity. Methods We analyzed the TCR repertoire of the major memory CD4+ and CD8+T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset, tissue, and individual were analyzed for clonal diversity, expansion and overlap between lineage, T cell subsets, and anatomic sites. TCR repertoires were further analyzed for TRBV gene usage and CDR3 edit distance. Results Across blood, lymphoid organs, and lungs, human memory, and effector CD8+T cells exhibit greater clonal expansion and distinct TRBV usage compared to CD4+T cell subsets. Extensive sharing of clones between tissues was observed for CD8+T cells; large clones specific to TEMRA cells were present in all sites, while TEM cells contained clones shared between sites and with TRM. For CD4+T cells, TEM clones exhibited the most sharing between sites, followed by TRM, while TCM clones were diverse with minimal sharing between sites and subsets. Within sites, TRM clones exhibited tissue-specific expansions, and maintained clonal diversity with age, compared to age-associated clonal expansions in circulating memory subsets. Edit distance analysis revealed tissue-specific biases in clonal similarity. Conclusions Our results show that the human memory T cell repertoire comprises clones which persist across ...
    Keywords Immunogenomics ; Immunology ; T cell ; Immunity ; Medicine ; R ; Genetics ; QH426-470
    Subject code 612
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19

    Michael Chait / Mine M. Yilmaz / Shanila Shakil / Amy W. Ku / Pranay Dogra / Thomas J. Connors / Peter A. Szabo / Joshua I. Gray / Steven B. Wells / Masaru Kubota / Rei Matsumoto / Maya M.L. Poon / Mark E. Snyder / Matthew R. Baldwin / Peter A. Sims / Anjali Saqi / Donna L. Farber / Stuart P. Weisberg

    JCI Insight, Vol 7, Iss

    2022  Volume 11

    Abstract: Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 ... ...

    Abstract Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18–92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19–mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.
    Keywords Aging ; COVID-19 ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

    Peter A. Szabo / Hanna Mendes Levitin / Michelle Miron / Mark E. Snyder / Takashi Senda / Jinzhou Yuan / Yim Ling Cheng / Erin C. Bush / Pranay Dogra / Puspa Thapa / Donna L. Farber / Peter A. Sims

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 16

    Abstract: Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a ... ...

    Abstract Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.
    Keywords Science ; Q
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

    Peter A. Szabo / Hanna Mendes Levitin / Michelle Miron / Mark E. Snyder / Takashi Senda / Jinzhou Yuan / Yim Ling Cheng / Erin C. Bush / Pranay Dogra / Puspa Thapa / Donna L. Farber / Peter A. Sims

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 16

    Abstract: Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a ... ...

    Abstract Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.
    Keywords Science ; Q
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Molecular programs of fibrotic change in aging human lung

    Seoyeon Lee / Mohammad Naimul Islam / Kaveh Boostanpour / Dvir Aran / Guangchun Jin / Stephanie Christenson / Michael A. Matthay / Walter L. Eckalbar / Daryle J. DePianto / Joseph R. Arron / Liam Magee / Sunita Bhattacharya / Rei Matsumoto / Masaru Kubota / Donna L. Farber / Jahar Bhattacharya / Paul J. Wolters / Mallar Bhattacharya

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Age is associated with increasing vulnerability to both acute and chronic lung diseases. Employing genomic analysis and live lung imaging, this study reveals a profile of increased cellular senescence, telomere shortening, and fibrosis-induced impaired ... ...

    Abstract Age is associated with increasing vulnerability to both acute and chronic lung diseases. Employing genomic analysis and live lung imaging, this study reveals a profile of increased cellular senescence, telomere shortening, and fibrosis-induced impaired alveolar function in the natural history of human lung aging.
    Keywords Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites

    Brahma V. Kumar / Wenji Ma / Michelle Miron / Tomer Granot / Rebecca S. Guyer / Dustin J. Carpenter / Takashi Senda / Xiaoyun Sun / Siu-Hong Ho / Harvey Lerner / Amy L. Friedman / Yufeng Shen / Donna L. Farber

    Cell Reports, Vol 20, Iss 12, Pp 2921-

    2017  Volume 2934

    Abstract: Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human ... ...

    Abstract Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69− TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8+ TRMs. Human TRMs in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced turnover compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together, our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.
    Keywords human immunology ; memory T cells ; RNA-seq ; mucosal immunity ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2017-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  9. Article ; Online: Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway

    Stuart P. Weisberg / Dustin J. Carpenter / Michael Chait / Pranay Dogra / Robyn D. Gartrell-Corrado / Andrew X. Chen / Sean Campbell / Wei Liu / Pooja Saraf / Mark E. Snyder / Masaru Kubota / Nichole M. Danzl / Beth A. Schrope / Raul Rabadan / Yvonne Saenger / Xiaojuan Chen / Donna L. Farber

    Cell Reports, Vol 29, Iss 12, Pp 3916-3932.e

    2019  Volume 5

    Abstract: Summary: Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the ... ...

    Abstract Summary: Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8+PD-1hi TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies. : Non-recirculating tissue-resident memory T cells (TRMs) mediate immune responses in non-lymphoid tissues. Using a human organ donor tissue resource, Weisberg et al. reveal that PD-1hi pancreas TRMs are regulated by PD-L1+ macrophages during homeostasis. Comparison with chronic pancreatitis patient samples shows how pancreas TRM regulation is altered during inflammation. Keywords: memory T cells, pancreas, chronic pancreatitis, tissue immunity, mucosal immunity, PD-1, macrophage
    Keywords Biology (General) ; QH301-705.5
    Subject code 616 ; 610
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  10. Article ; Online: Increased memory conversion of naïve CD8 T cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure.

    Georgia Fousteri / Amy Dave / Amy Juedes / Therese Juntti / Bret Morin / Lisa Togher / Donna L Farber / Matthias von Herrath

    PLoS ONE, Vol 6, Iss 1, p e

    2011  Volume 14502

    Abstract: Memory CD8 T cells form an essential part of protective immunity against viral infections. Antigenic load, costimulation, CD4-help, cytokines and chemokines fluctuate during the course of an antiviral immune response thus affecting CD8 T cell activation ... ...

    Abstract Memory CD8 T cells form an essential part of protective immunity against viral infections. Antigenic load, costimulation, CD4-help, cytokines and chemokines fluctuate during the course of an antiviral immune response thus affecting CD8 T cell activation and memory conversion.In the present study, naïve TCR transgenic LCMV-specific P14 CD8 T cells engaged at a late stage during the acute antiviral LCMV response showed reduced expansion kinetics but greater memory conversion in the spleen. Such late activated cells displayed a memory precursor effector phenotype already at the peak of the systemic antiviral response, suggesting that the environment determined their fate during antigen encounter. In the spleen, the majority of late transferred cells exhibited a central memory phenotype compared to the effector memory displayed by the early transferred cells. Increasing the inflammatory response by exogenous administration of IFNγ, PolyI:C or CpG did not affect memory conversion in the late transferred group, suggesting that the diverging antigen load early versus later during acute infection had determined their fate. In agreement, reduction in the LCMV antigenic load after ribavirin treatment enhanced the contribution of early transferred cells to the long lasting memory pool.Our results show that naïve CD8 cells, exposed to reduced duration or concentration of antigen during viral infection convert into memory more efficiently, an observation that could have significant implications for vaccine design.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top