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Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
    • بيانات النشر:
      Publication: Basingstoke : Nature Publishing Group
      Original Publication: London, Macmillan Journals ltd.
    • الموضوع:
      Apoptosis* ; Phagocytosis*; Bronchi/*cytology ; Epithelial Cells/*physiology ; Inflammation/*pathology ; Lung/*pathology ; Respiratory Hypersensitivity/*pathology; Allergens/immunology ; Animals ; Bronchi/immunology ; Bronchi/pathology ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/immunology ; Dust/immunology ; Epithelial Cells/immunology ; Immunity, Innate/immunology ; Inflammation/immunology ; Interleukin-10/biosynthesis ; Interleukin-10/immunology ; Interleukin-33 ; Interleukins/biosynthesis ; Interleukins/immunology ; Lung/immunology ; Mice ; Ovalbumin/immunology ; Pyroglyphidae/immunology ; Respiratory Hypersensitivity/immunology ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Up-Regulation ; rac1 GTP-Binding Protein/deficiency ; rac1 GTP-Binding Protein/genetics ; rac1 GTP-Binding Protein/metabolism
    • نبذة مختصرة :
      Lung epithelial cells can influence immune responses to airway allergens. Airway epithelial cells also undergo apoptosis after encountering environmental allergens; yet, relatively little is known about how these are cleared, and their effect on airway inflammation. Here we show that airway epithelial cells efficiently engulf apoptotic epithelial cells and secrete anti-inflammatory cytokines, dependent upon intracellular signalling by the small GTPase Rac1. Inducible deletion of Rac1 expression specifically in airway epithelial cells in a mouse model resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract or ovalbumin as allergens led to exacerbated inflammation, augmented Th2 cytokines and airway hyper-responsiveness, with decreased interleukin (IL)-10 in bronchial lavages. Rac1-deficient epithelial cells produced much higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of nuocyte-like cells. Administration of exogenous IL-10 'rescued' the airway inflammation phenotype in Rac1-deficient mice, with decreased IL-33. Collectively, these genetic and functional studies suggest a new role for Rac1-dependent engulfment by airway epithelial cells and in establishing the anti-inflammatory environment, and that defects in cell clearance in the airways could contribute to inflammatory responses towards common allergens.
    • Comments:
      Comment in: Nat Rev Immunol. 2013 Mar;13(3):157. (PMID: 23391994)
    • References:
      Nat Immunol. 2002 Jul;3(7):673-80. (PMID: 12055625)
      Cell. 2010 Mar 19;140(6):777-83. (PMID: 20303868)
      Thorax. 1962 Mar;17:69-72. (PMID: 14478653)
      Nat Med. 2009 Apr;15(4):410-6. (PMID: 19330007)
      Trends Mol Med. 2010 Jul;16(7):321-8. (PMID: 20605742)
      Pediatr Allergy Immunol. 2004 Apr;15(2):159-62. (PMID: 15059193)
      J Exp Med. 2002 Dec 16;196(12):1645-51. (PMID: 12486107)
      Curr Opin Immunol. 2010 Dec;22(6):800-6. (PMID: 21071194)
      Expert Rev Clin Immunol. 2009 May;5(3):233-7. (PMID: 20477001)
      Nat Med. 2012 May 04;18(5):684-92. (PMID: 22561832)
      Cell Death Differ. 2005 Feb;12(2):107-14. (PMID: 15647754)
      Nat Rev Immunol. 2007 Dec;7(12):964-74. (PMID: 18037898)
      Apoptosis. 1999 Dec;4(6):407-17. (PMID: 14634325)
      J Biol Chem. 2007 Dec 7;282(49):35666-78. (PMID: 17932039)
      J Clin Invest. 1998 Feb 15;101(4):890-8. (PMID: 9466984)
      J Allergy (Cairo). 2011;2011:948406. (PMID: 22203854)
      Transgenic Res. 2002 Feb;11(1):21-9. (PMID: 11874100)
      J Immunol. 2003 Jun 1;170(11):5652-7. (PMID: 12759446)
      Nature. 2009 Jan 29;457(7229):585-8. (PMID: 19060881)
      Nat Rev Immunol. 2010 Feb;10(2):103-10. (PMID: 20081870)
      Curr Biol. 2009 Feb 24;19(4):346-51. (PMID: 19217291)
      J Allergy Clin Immunol. 2012 Jan;129(1):191-8.e1-4. (PMID: 22079492)
      Am J Respir Crit Care Med. 2011 Aug 15;184(4):390-2. (PMID: 21844510)
      J Immunol. 2004 Nov 15;173(10):6384-92. (PMID: 15528378)
      Immunity. 2011 Oct 28;35(4):445-55. (PMID: 22035837)
      Ann N Y Acad Sci. 2010 Oct;1209:30-6. (PMID: 20958313)
      J Allergy Clin Immunol. 1996 Jun;97(6):1288-96. (PMID: 8648025)
      Nature. 2011 Aug 21;477(7363):220-4. (PMID: 21857682)
      J Virol. 2008 Nov;82(22):11294-307. (PMID: 18787012)
      Blood. 2007 Apr 1;109(7):2854-62. (PMID: 17119109)
    • Grant Information:
      R01 AI057438 United States AI NIAID NIH HHS; T32 AI007496 United States AI NIAID NIH HHS; U01 AI100799 United States AI NIAID NIH HHS
    • الرقم المعرف:
      0 (Allergens)
      0 (Dust)
      0 (Il33 protein, mouse)
      0 (Interleukin-33)
      0 (Interleukins)
      130068-27-8 (Interleukin-10)
      9006-59-1 (Ovalbumin)
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
    • الموضوع:
      Date Created: 20121214 Date Completed: 20130304 Latest Revision: 20211021
    • الموضوع:
      20240829
    • الرقم المعرف:
      PMC3662023
    • الرقم المعرف:
      10.1038/nature11714
    • الرقم المعرف:
      23235830