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  • 1
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    Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-03-26
    Description: Regulatory T cells (T(reg)) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of T(reg) cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (T(H)17). Although T(reg) cell dysfunction and/or T(H)17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of T(reg) and T(H)17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional T(reg) cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with T(reg) cell development, boosted T(H)17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both T(reg) and T(H)17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quintana, Francisco J -- Basso, Alexandre S -- Iglesias, Antonio H -- Korn, Thomas -- Farez, Mauricio F -- Bettelli, Estelle -- Caccamo, Mario -- Oukka, Mohamed -- Weiner, Howard L -- AI435801/AI/NIAID NIH HHS/ -- NS38037/NS/NINDS NIH HHS/ -- P01 NS038037/NS/NINDS NIH HHS/ -- R01 AI073542/AI/NIAID NIH HHS/ -- R01 AI073542-01/AI/NIAID NIH HHS/ -- R01 AI073542-02/AI/NIAID NIH HHS/ -- R01 NS059996/NS/NINDS NIH HHS/ -- R01AI073542-01/AI/NIAID NIH HHS/ -- England -- Nature. 2008 May 1;453(7191):65-71. doi: 10.1038/nature06880. Epub 2008 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18362915" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbazoles/metabolism/pharmacology ; *Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/chemically induced/immunology ; Forkhead Transcription Factors/genetics/metabolism ; Humans ; Indoles/metabolism/pharmacology ; Interleukin-17/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; T-Lymphocytes, Helper-Inducer/*cytology/drug effects/*metabolism ; T-Lymphocytes, Regulatory/*cytology/drug effects/*metabolism ; Tetrachlorodibenzodioxin/metabolism/pharmacology ; Transforming Growth Factor beta1/immunology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Transformation of Generation Processes From Small Runoff Events to Large Floods (2021)
    Details
    Publication Date: 2021-07-03
    Description: Mixture of runoff generation processes poses a challenge for predicting upper flood quantiles. We examined transformations of generation processes from all identifiable runoff events to frequent and upper tail floods for a large set of mesoscale catchments and observed a substantial change of the dominant processes. Two trajectories of transformation were detected. In regions where floods occur almost exclusively in winter the dominance of processes related to snowmelt consistently increases from small events to frequent and upper tail floods. In catchments characterized by frequent winter‐spring floods and occasional summer‐autumn flood events triggered by rare meteorological phenomena (e.g., Vb cyclones), processes that dominate upper tails are not adequately represented in the sample of frequent floods. Predictions of extremes and projections of flood changes might remain highly uncertain in the latter cases.
    Description: Plain Language Summary: Prediction of floods remains a challenging task for the engineering practice. Floods triggered by different physical mechanisms have contrasting statistical attributes. Mixture of these processes hinders reliable prediction of the largest floods. In this study we classified a large number of streamflow events observed in a wide range of German river basins according to their generation processes. We analyzed changes in the frequency of occurrence of different generation processes, from the smallest identifiable runoff events to annual floods to rarer events corresponding to larger river flows. Interestingly, for some river basins certain processes tend to consistently increase their frequency from small streamflow events to common and larger floods. In other cases, we observed an opposite tendency. Certain processes become less important for the generation of annual floods compared to small streamflow events but then dominate generation of the largest floods. This has important implications for our ability to predict extreme floods and their possible changes.
    Description: Key Points: We analyzed transformation of processes from small runoff events to larger floods using a process‐based framework for event characterization. A substantial transformation of the frequency of processes from small runoff events to frequent and upper tail floods is observed. Differences in trajectories of process transformation among catchments suggest regionally variable predictability of extremes.
    Description: Deutsche Forschungsgemeinschaft (DFG) http://dx.doi.org/10.13039/501100001659
    Description: Helmholtz‐Zentrum für Umweltforschung (UFZ)
    Keywords: 551.489 ; flood origins ; event classification ; ordinary events ; annual floods ; upper tail floods ; process transformation
    Type: article
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