Immunity, inflammation, and remodeling in the airway epithelial barrier: Epithelial-viral-allergic paradigm

Michael J. Holtzman, Jeffrey D. Morton, Laurie P. Shornick, Jeffrey Tyner, Mary P. O'Sullivan, Aurita Antao, Mindy Lo, Mario Castro, Michael J. Walter

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The concept that airway inflammation leads to airway disease has led to a widening search for the types of cellular and molecular interactions responsible for linking the initial stimulus to the final abnormality in airway function. It has not yet been possible to integrate all of this information into a single model for the development of airway inflammation and remodeling, but a useful framework has been based on the behavior of the adaptive immune system. In that paradigm, an exaggeration of T-helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli leads to airway inflammatory disease, especially asthma. In this review, we summarize alternative evidence that the innate immune system, typified by actions of airway epithelial cells and macrophages, may also be specially programmed for antiviral defense and abnormally programmed in inflammatory disease. Furthermore, this abnormality may be inducible by paramyxoviral infection and, in the proper genetic background, may persist indefinitely. Taken together, we propose a new model that highlights specific interactions between epithelial, viral, and allergic components and so better explains the basis for airway immunity, inflammation, and remodeling in response to viral infection and the development of long-term disease phenotypes typical of asthma and other hypersecretory airway diseases.

Original languageEnglish (US)
Pages (from-to)19-46
Number of pages28
JournalPhysiological Reviews
Volume82
Issue number1
StatePublished - 2002
Externally publishedYes

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Airway Remodeling
Immunity
Inflammation
Immune System
Asthma
Viral Structures
Psychological Adaptation
Virus Diseases
Antiviral Agents
Epithelial Cells
Macrophages
Phenotype
Infection

ASJC Scopus subject areas

  • Physiology

Cite this

Holtzman, M. J., Morton, J. D., Shornick, L. P., Tyner, J., O'Sullivan, M. P., Antao, A., ... Walter, M. J. (2002). Immunity, inflammation, and remodeling in the airway epithelial barrier: Epithelial-viral-allergic paradigm. Physiological Reviews, 82(1), 19-46.

Immunity, inflammation, and remodeling in the airway epithelial barrier : Epithelial-viral-allergic paradigm. / Holtzman, Michael J.; Morton, Jeffrey D.; Shornick, Laurie P.; Tyner, Jeffrey; O'Sullivan, Mary P.; Antao, Aurita; Lo, Mindy; Castro, Mario; Walter, Michael J.

In: Physiological Reviews, Vol. 82, No. 1, 2002, p. 19-46.

Research output: Contribution to journalArticle

Holtzman, MJ, Morton, JD, Shornick, LP, Tyner, J, O'Sullivan, MP, Antao, A, Lo, M, Castro, M & Walter, MJ 2002, 'Immunity, inflammation, and remodeling in the airway epithelial barrier: Epithelial-viral-allergic paradigm', Physiological Reviews, vol. 82, no. 1, pp. 19-46.
Holtzman, Michael J. ; Morton, Jeffrey D. ; Shornick, Laurie P. ; Tyner, Jeffrey ; O'Sullivan, Mary P. ; Antao, Aurita ; Lo, Mindy ; Castro, Mario ; Walter, Michael J. / Immunity, inflammation, and remodeling in the airway epithelial barrier : Epithelial-viral-allergic paradigm. In: Physiological Reviews. 2002 ; Vol. 82, No. 1. pp. 19-46.
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