CD4+ T cell-dependent airway mucus production occurs in response to IL-5 expression in lung

J. Paul Justice, J. Crosby, M. T. Borchers, A. Tomkinson, J. J. Lee, N. A. Lee

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The potential role of airway interleukin-5 (IL-5) expression in eliciting mucus production was demonstrated in a pulmonary IL-5 transgenic mouse model (NJ.1726) in which naive transgenic mice display comparable levels of airway mucus relative to allergen-sensitized and -challenged wild-type mice. The intrinsic mucus accumulation of NJ.1726 was abolished in compound transgenic-gene knockout mice deficient of either CD4+ cells [NJ.1726/CD4(-/-)] or αβ T cell receptor-positive (TCR+) cells [NJ.1726/αβ TCR(-/-)]. In addition, mucus production in naive NJ.1726 was inhibited by >90% after administration of the soluble anti-IL-4 receptor α-subunit antagonist. The loss of mucus production in NJ.1726/CD4(-/-), NJ.1726/αβ TCR(-/-), and anti-IL-4 receptor α-subunit antagonist-treated mice occurred notwithstanding the significant pulmonary eosinophilia and expansion of airway B cells induced by ectopic IL-5 expression. Furthermore, the loss of mucus accumulation occurred in these mice despite elevated levels of airway and peripheral IL-5, indicating that IL-5 does not directly induce goblet cell metaplasia and mucus production. Thus pulmonary expression of IL-5 alone is capable of inducing CD4+ T cell-dependent goblet cell metaplasia, apparently mediated by IL-4 receptor α-subunit-ligand interactions, and represents a previously unrecognized novel pathway for augmenting allergen-induced mucus production.

Original languageEnglish (US)
Pages (from-to)L1066-L1074
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number5 26-5
StatePublished - Jun 29 2002

Keywords

  • Asthma
  • Gene knockout
  • Goblet cell
  • Transgenic

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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