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  • Proceedings of the National Academy of Sciences  (4)
  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 15 ( 2007-04-10), p. 6478-6483
    Abstract: Understanding plant metabolism as an integrated system is essential for metabolic engineering aimed at the effective production of compounds useful to human life and the global environment. The “omics” approach integrates transcriptome and metabolome data into a single data set and can lead to the identification of unknown genes and their regulatory networks involved in metabolic pathways of interest. One of the intriguing, although poorly described metabolic pathways in plants is the biosynthesis of glucosinolates (GSLs), a group of bioactive secondary products derived from amino acids that are found in the family Brassicaceae. Here we report the discovery of two R2R3-Myb transcription factors that positively control the biosynthesis of GSLs in Arabidopsis thaliana by an integrated omics approach. Combined transcriptome coexpression analysis of publicly available, condition-independent data and the condition-specific (i.e., sulfur-deficiency) data identified Myb28 and Myb29 as candidate transcription factor genes specifically involved in the regulation of aliphatic GSL production. Analysis of a knockout mutant and ectopic expression of the gene demonstrated that Myb28 is a positive regulator for basal-level production of aliphatic GSLs. Myb29 presumably plays an accessory function for methyl jasmonate-mediated induction of a set of aliphatic GSL biosynthetic genes. Overexpression of Myb28 in Arabidopsis -cultured suspension cells, which do not normally synthesize GSLs, resulted in the production of large amounts of GSLs, suggesting the possibility of efficient industrial production of GSLs by manipulation of these transcription factors. A working model for regulation of GSL production involving these genes, renamed Production of Methionine-Derived Glucosinolate ( PMG ) 1 and 2 , are postulated.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 20 ( 2016-05-17)
    Abstract: Memory CD4 + T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1 + IL-7–producing lymphatic endothelial cells (LECs). The Thy1 + IL-7–producing LECs express IL-33 and T-cell–attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4 + T cells and IL-7 + IL-33 + LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1 + IL-7–producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 9 ( 2016-03), p. 2460-2465
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 9 ( 2016-03), p. 2460-2465
    Abstract: The Fas/FasL (CD95/CD178) system is required for immune regulation; however, it is unclear in which cells, when, and where Fas/FasL molecules act in the immune system. We found that CD8 + CD122 + cells, which are mostly composed of memory T cells in comparison with naïve cells in the CD8 + CD122 − population, were previously shown to include cells with regulatory activity and could be separated into CD49d low cells and CD49d high cells. We established in vitro and in vivo experimental systems to evaluate the regulatory activity of CD122 + cells. Regulatory activity was observed in CD8 + CD122 + CD49d low but not in CD8 + CD122 + CD49d high cells, indicating that the regulatory cells in the CD8 + CD122 + population could be narrowed down to CD49d low cells. CD8 + CD122 − cells taken from lymphoproliferation ( lpr ) mice were resistant to regulation by normal CD122 + Tregs. CD122 + Tregs taken from generalized lymphoproliferative disease ( gld ) mice did not regulate wild-type CD8 + CD122 − cells, indicating that the regulation by CD122 + Tregs is Fas/FasL-dependent. CD122 + Tregs taken from IL-10–deficient mice could regulate CD8 + CD122 − cells as equally as wild-type CD122 + Tregs both in vitro and in vivo. MHC class I-missing T cells were not regulated by CD122 + Tregs in vitro. CD122 + Tregs also regulated CD4 + cells in a Fas/FasL-dependent manner in vitro. These results suggest an essential role of Fas/FasL as a terminal effector of the CD122 + Tregs that kill activated T cells to maintain immune homeostasis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 9 ( 2022-03)
    Abstract: Mounting evidence suggests that nematode infection can protect against disorders of immune dysregulation. Administration of live parasites or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for immune disorders, including asthma. Human clinical trials of live parasite ingestion for the treatment of immune disorders have produced promising results, yet concerns persist regarding the ingestion of pathogenic organisms and the immunogenicity of protein components. Despite extensive efforts to define the active components of ES products, no small molecules with immune regulatory activity have been identified from nematodes. Here we show that an evolutionarily conserved family of nematode pheromones called ascarosides strongly modulates the pulmonary immune response and reduces asthma severity in mice. Screening the inhibitory effects of ascarosides produced by animal-parasitic nematodes on the development of asthma in an ovalbumin (OVA) murine model, we found that administration of nanogram quantities of ascr#7 prevented the development of lung eosinophilia, goblet cell metaplasia, and airway hyperreactivity. Ascr#7 suppressed the production of IL-33 from lung epithelial cells and reduced the number of memory-type pathogenic Th2 cells and ILC2s in the lung, both key drivers of the pathology of asthma. Our findings suggest that the mammalian immune system recognizes ascarosides as an evolutionarily conserved molecular signature of parasitic nematodes. The identification of a nematode-produced small molecule underlying the well-documented immunomodulatory effects of ES products may enable the development of treatment strategies for allergic diseases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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