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TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology
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نویسنده
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kannan y. ,perez-lloret j. ,li y. ,entwistle l.j. ,khoury h. ,papoutsopoulou s. ,mahmood r. ,mansour n.r. ,ching-cheng huang s. ,pearce e.j. ,pedro s. de carvalho l. ,ley s.c. ,wilson m.s.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 8
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چکیده
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Persistent th2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. despite a good understanding of the cellular mechanisms involved in fibrogenesis,there are very few therapeutic options available,highlighting a significant medical need and gap in our understanding of the molecular mechanisms of th2-mediated immunopathology. in this study,we found that the map3 kinase,tpl-2 (map3k8; cot) regulated th2-mediated intestinal,hepatic and pulmonary immunopathology following schistosoma mansoni infection or s. mansoni egg injection. elevated inflammation,th2 cell responses and exacerbated fibrosis in map3k8–/–mice was observed in mice with myeloid cell-specific (lysm) deletion of map3k8,but not cd4 cell-specific deletion of map3k8,indicating that tpl-2 regulated myeloid cell function to limit th2-mediated immunopathology. transcriptional and metabolic assays of map3k8–/–m2 macrophages identified that tpl-2 was required for lipolysis,m2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. taken together this study identified that tpl-2 regulated th2-mediated inflammation by supporting lipolysis and m2 macrophage activation,preventing th2 cell expansion and downstream immunopathology and fibrosis. © 2016 kannan et al.
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آدرس
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allergy and anti-helminth immunity laboratory,the francis crick institute,london, United Kingdom, allergy and anti-helminth immunity laboratory,the francis crick institute,london, United Kingdom, allergy and anti-helminth immunity laboratory,the francis crick institute,london, United Kingdom, allergy and anti-helminth immunity laboratory,the francis crick institute,london, United Kingdom, mycobacterial metabolism and antibiotic research laboratory,the francis crick institute,london, United Kingdom, immune cell signaling laboratory,the francis crick institute,london,united kingdom,faculty of life sciences,university of manchester,manchester, United Kingdom, experimental histopathology,mill hill laboratory,the francis crick institute,london, United Kingdom, department of infection and immunity,london school of hygiene and tropical medicine,london, United Kingdom, department of pathology and immunology,washington university school of medicine,st. louis,mo, United States, department of pathology and immunology,washington university school of medicine,st. louis,mo,united states,faculty of biology,university of freiburg,and department of immunometabolism,max planck institute of immunobiology and epigenetics,freiburg, Germany, mycobacterial metabolism and antibiotic research laboratory,the francis crick institute,london, United Kingdom, immune cell signaling laboratory,the francis crick institute,london, United Kingdom, allergy and anti-helminth immunity laboratory,the francis crick institute,london, United Kingdom
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Authors
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