Control of epithelial immune-response genes and implications for airway immunity and inflammation

M. J. Holtzman, D. C. Look, D. Sampath, M. Castro, T. Koga, M. J. Walter

Research output: Contribution to journalReview article

25 Scopus citations

Abstract

A major goal of our research is to understand how immune cells (especially T cells) infiltrate the pulmonary airway during host defense and inflammatory disease (especially asthma). In that context, we have proposed that epithelial cells lining the airway provide critical biochemical signals for immune-cell influx and activation and that this epithelial-immune celt interaction is a critical feature of airway inflammation and hyperreactivity. In this brief report, we describe our progress in defining a subset of epithelial immune-response genes the expression of which is coordinated for vital defense both directly in response to replicating virus and indirectly under the control of a specific interferon-gamma signal transduction pathway featuring the Stat1 transcription factor as a critical relay signal between cytoplasm and nucleus. Unexpectedly, the same pathway is also activated during asthmatic airway inflammation in a setting where there is no apparent infection and no increase in interferon-gamma levels. The findings provide the first evidence of an overactive Stat1-dependent gene network in asthmatic airways and a novel molecular link between mucosal immunity and inflammation. The findings also offer the possibility that overactivity of Stat1-dependent genes might augment a subsequent T helper cell (Th1)-type response to virus or might combine with a heightened Th2-type response to allergen to account for more severe exacerbations of asthma.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalProceedings of the Association of American Physicians
Volume110
Issue number1
StatePublished - Feb 6 1998

Keywords

  • Airway epithelial cell
  • Asthma
  • Cell adhesion molecule
  • Chemokine
  • T cell
  • Transcription factor

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