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10.1371/journal.pone.0079340

http://scihub22266oqcxt.onion/10.1371/journal.pone.0079340
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suck abstract from ncbi


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pmid24223177
      PLoS+One 2013 ; 8 (11 ): e79340
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  • ADAM17-mediated processing of TNF-? expressed by antiviral effector CD8+ T cells is required for severe T-cell-mediated lung injury #MMPMID24223177
  • DeBerge MP ; Ely KH ; Cheng GS ; Enelow RI
  • PLoS One 2013[]; 8 (11 ): e79340 PMID24223177 show ga
  • Influenza infection in humans evokes a potent CD8(+) T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8(+) T-cell expression of TNF-? is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-? is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-? processing in CD8(+) T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-? by CD8(+) T cells significantly attenuated the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. This was due in part to diminished chemokine expression, as TNF-? processing was required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. We confirmed the importance of CXCL2 expression in acute lung injury by transferring influenza-specific CD8(+) T cells into transgenic mice lacking CXCR2. These mice exhibited reduced airway infiltration, attenuated lung injury, and enhanced survival. Theses studies describe a critical role for TNF-? processing by CD8(+) T cells in the initiation and severity of acute lung injury, which may have important implications for limiting immunopathology during influenza infection and other human infectious or inflammatory diseases.
  • |*Gene Expression Regulation [MESH]
  • |*Proteolysis [MESH]
  • |ADAM Proteins/deficiency/*metabolism [MESH]
  • |ADAM17 Protein [MESH]
  • |Animals [MESH]
  • |CD8-Positive T-Lymphocytes/*immunology [MESH]
  • |Epithelial Cells/metabolism/pathology [MESH]
  • |Female [MESH]
  • |Humans [MESH]
  • |Lung Injury/*immunology/metabolism/pathology/*virology [MESH]
  • |Lung/immunology/metabolism/pathology/virology [MESH]
  • |Macrophages/immunology [MESH]
  • |Mice [MESH]
  • |Neutrophil Infiltration [MESH]
  • |Receptors, Interleukin-8B/metabolism [MESH]
  • |Signal Transduction [MESH]
  • |Solubility [MESH]


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