ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2011-03-29
    Description: CD4(+) T helper lymphocytes that express interleukin-17 (T(H)17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in T(H)17 cell differentiation and function with susceptibility to Crohn's disease, rheumatoid arthritis and psoriasis. Thus, the pathway towards differentiation of T(H)17 cells and, perhaps, of related innate lymphoid cells with similar effector functions, is an attractive target for therapeutic applications. Mouse and human T(H)17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor RORgammat, which is required for induction of IL-17 transcription and for the manifestation of T(H)17-dependent autoimmune disease in mice. By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of RORgammat transcriptional activity. Digoxin inhibited murine T(H)17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives 20,22-dihydrodigoxin-21,23-diol and digoxin-21-salicylidene specifically inhibited induction of IL-17 in human CD4(+) T cells. Using these small-molecule compounds, we demonstrate that RORgammat is important for the maintenance of IL-17 expression in mouse and human effector T cells. These data indicate that derivatives of digoxin can be used as chemical templates for the development of RORgammat-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172133/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huh, Jun R -- Leung, Monica W L -- Huang, Pengxiang -- Ryan, Daniel A -- Krout, Michael R -- Malapaka, Raghu R V -- Chow, Jonathan -- Manel, Nicolas -- Ciofani, Maria -- Kim, Sangwon V -- Cuesta, Adolfo -- Santori, Fabio R -- Lafaille, Juan J -- Xu, H Eric -- Gin, David Y -- Rastinejad, Fraydoon -- Littman, Dan R -- 2R01GM55217/GM/NIGMS NIH HHS/ -- F32GM0860552/GM/NIGMS NIH HHS/ -- R01 AI080885/AI/NIAID NIH HHS/ -- R01AI080885/AI/NIAID NIH HHS/ -- R01GM058833/GM/NIGMS NIH HHS/ -- R01GM067659/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Apr 28;472(7344):486-90. doi: 10.1038/nature09978. Epub 2011 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21441909" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoimmune Diseases/drug therapy/immunology/pathology ; Autoimmunity/drug effects/immunology ; Cell Differentiation/*drug effects ; Cell Line ; Digoxin/*analogs & derivatives/chemistry/metabolism/*pharmacology/therapeutic use ; Drosophila/cytology ; Humans ; Interleukin-17/biosynthesis/immunology ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3/*antagonists & ; inhibitors/metabolism ; Th17 Cells/*cytology/*drug effects/immunology ; Transcription, Genetic/drug effects/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2016-01-30
    Description: Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Gloria B -- Yim, Yeong S -- Wong, Helen -- Kim, Sangdoo -- Kim, Hyunju -- Kim, Sangwon V -- Hoeffer, Charles A -- Littman, Dan R -- Huh, Jun R -- F31 NS083277/NS/NINDS NIH HHS/ -- F31NS083277/NS/NINDS NIH HHS/ -- R00 DK091508/DK/NIDDK NIH HHS/ -- R00DK091508/DK/NIDDK NIH HHS/ -- R01 NS086933/NS/NINDS NIH HHS/ -- R01NS086933/NS/NINDS NIH HHS/ -- T32 AI100853/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 26;351(6276):933-9. doi: 10.1126/science.aad0314. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Center for Neural Science, New York University, New York, NY 10003, USA. Institute for Behavioral Genetics, Department of Integrated Physiology, University of Colorado, Boulder, CO 80303, USA. ; Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. ; Center for Neural Science, New York University, New York, NY 10003, USA. Institute for Behavioral Genetics, Department of Integrated Physiology, University of Colorado, Boulder, CO 80303, USA. charles.hoeffer@colorado.edu dan.littman@med.nyu.edu jun.huh@umassmed.edu. ; The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Howard Hughes Medical Institute, New York, NY 10016, USA. charles.hoeffer@colorado.edu dan.littman@med.nyu.edu jun.huh@umassmed.edu. ; Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. charles.hoeffer@colorado.edu dan.littman@med.nyu.edu jun.huh@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26822608" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...