CD4(+) T cell-dependent airway mucus production occurs in response to IL-5 expression in lung.
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 alphabeta T cell receptor-positive (TCR(+)) cells [NJ.1726/alphabeta TCR(-/-)]. In addition, mucus production in naive NJ.1726 was inhibited by >90% after administration of the soluble anti-IL-4 receptor alpha-subunit antagonist. The loss of mucus production in NJ.1726/CD4(-/-), NJ.1726/alphabeta TCR(-/-), and anti-IL-4 receptor alpha-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 alpha-subunit-ligand interactions, and represents a previously unrecognized novel pathway for augmenting allergen-induced mucus production.
Justice
J Paul
JP
Divisions of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA.
Crosby
J
J
Borchers
M T
MT
Tomkinson
A
A
Lee
J J
JJ
Lee
N A
NA
D000485:Allergens / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D020397:Goblet Cells / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000378:metabolism
D000485:Allergens; D015848:Interleukin-5; D010047:Ovalbumin