Interference with intraepithelial TNF-α signaling inhibits CD8 + T-cell-mediated lung injury in influenza infection

Anon Srikiatkhachorn, Jyothi Chintapalli, Jun Liu, Mohammad Jamaluddin, Kevin S. Harrod, Jeffrey A. Whitsett, Richard I. Enelow, Chilakamarti V. Ramana

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

CD8+ T-cell-mediated pulmonary immunopathology in respiratory virus infection is mediated in large part by antigen-specific TNF-α expression by antiviral effector T cells, which results in epithelial chemokine expression and inflammatory infiltration of the lung. To further define the signaling events leading to lung epithelial chemokine production in response to CD8+ T-cell antigen recognition, we expressed the adenoviral 14.7K protein, a putative inhibitor of TNF-α signaling, in the distal lung epithelium, and analyzed the functional consequences. Distal airway epithelial expression of 14.7K resulted in a significant reduction in lung injury resulting from severe influenza pneumonia. In vitro analysis demonstrated a significant reduction in the expression of an important mediator of injury, CCL2, in response to CD8+ T-cell recognition, or to TNF-α. The inhibitory effect of 14.7K on CCL2 expression resulted from attenuation of NF-κB activity, which was independent of Iκ-Bα degradation or nuclear translocation of the p65 subunit. Furthermore, epithelial 14.7K expression inhibited serine phosphorylation of Akt, GSK-3β, and the p65 subunit of NF-κB, as well as recruitment of NF-κB for DNA binding in vivo. These results provide insight into the mechanism of 14.7K inhibition of NF-κB activity, as well as further elucidate the mechanisms involved in the induction of T-cell-mediated immunopathology in respiratory virus infection.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalViral Immunology
Volume23
Issue number6
DOIs
StatePublished - Dec 1 2010

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Lung Injury
Human Influenza
T-Lymphocytes
Infection
Lung
Virus Diseases
Chemokines
Respiratory Tract Infections
Glycogen Synthase Kinase 3
Viral Tumor Antigens
Serine
Antiviral Agents
Pneumonia
Epithelium
Phosphorylation
Antigens
DNA
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Molecular Medicine

Cite this

Srikiatkhachorn, A., Chintapalli, J., Liu, J., Jamaluddin, M., Harrod, K. S., Whitsett, J. A., ... Ramana, C. V. (2010). Interference with intraepithelial TNF-α signaling inhibits CD8 + T-cell-mediated lung injury in influenza infection. Viral Immunology, 23(6), 639-645. https://doi.org/10.1089/vim.2010.0076

Interference with intraepithelial TNF-α signaling inhibits CD8 + T-cell-mediated lung injury in influenza infection. / Srikiatkhachorn, Anon; Chintapalli, Jyothi; Liu, Jun; Jamaluddin, Mohammad; Harrod, Kevin S.; Whitsett, Jeffrey A.; Enelow, Richard I.; Ramana, Chilakamarti V.

In: Viral Immunology, Vol. 23, No. 6, 01.12.2010, p. 639-645.

Research output: Contribution to journalArticle

Srikiatkhachorn, A, Chintapalli, J, Liu, J, Jamaluddin, M, Harrod, KS, Whitsett, JA, Enelow, RI & Ramana, CV 2010, 'Interference with intraepithelial TNF-α signaling inhibits CD8 + T-cell-mediated lung injury in influenza infection', Viral Immunology, vol. 23, no. 6, pp. 639-645. https://doi.org/10.1089/vim.2010.0076
Srikiatkhachorn A, Chintapalli J, Liu J, Jamaluddin M, Harrod KS, Whitsett JA et al. Interference with intraepithelial TNF-α signaling inhibits CD8 + T-cell-mediated lung injury in influenza infection. Viral Immunology. 2010 Dec 1;23(6):639-645. https://doi.org/10.1089/vim.2010.0076
Srikiatkhachorn, Anon ; Chintapalli, Jyothi ; Liu, Jun ; Jamaluddin, Mohammad ; Harrod, Kevin S. ; Whitsett, Jeffrey A. ; Enelow, Richard I. ; Ramana, Chilakamarti V. / Interference with intraepithelial TNF-α signaling inhibits CD8 + T-cell-mediated lung injury in influenza infection. In: Viral Immunology. 2010 ; Vol. 23, No. 6. pp. 639-645.
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