Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair

Netanya G. Sandler, Margaret M. Mentink-Kane, Allen W. Cheever, Thomas A. Wynn

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens of MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis.

Original languageEnglish (US)
Pages (from-to)3655-3667
Number of pages13
JournalJournal of Immunology
Volume171
Issue number7
StatePublished - Oct 1 2003
Externally publishedYes

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Transcriptome
Pneumonia
Collagen
Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinases
Fibrosis
Matrix Metalloproteinase Inhibitors
Cytokines
Granuloma
Wound Healing
Genes
Pathology
Arginase
Chitinases
Interleukin-13
Schistosoma mansoni
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Interleukin-10
Eggs

ASJC Scopus subject areas

  • Immunology

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Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. / Sandler, Netanya G.; Mentink-Kane, Margaret M.; Cheever, Allen W.; Wynn, Thomas A.

In: Journal of Immunology, Vol. 171, No. 7, 01.10.2003, p. 3655-3667.

Research output: Contribution to journalArticle

Sandler, Netanya G. ; Mentink-Kane, Margaret M. ; Cheever, Allen W. ; Wynn, Thomas A. / Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. In: Journal of Immunology. 2003 ; Vol. 171, No. 7. pp. 3655-3667.
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