Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils.
Mucus hyperproduction in asthma results from airway inflammation and contributes to clinical symptoms, airway obstruction, and mortality. In human asthmatics and in animal models, excess mucus production correlates with airway eosinophilia. We previously described a system in which TCR transgenic CD4 Th2 cells generated in vitro were transferred into recipient mice and activated in the respiratory tract with inhaled Ag. Th2 cells stimulated airway eosinophilia and a marked increase in mucus production, while mice that received Th1 cells exhibited airway inflammation without eosinophilia or mucus. Mucus could be induced by IL-4-/- Th2 cells at comparable levels to mucus induced by IL-4+/+ Th2 cells. In the current studies we dissect further the mechanisms of Th2-induced mucus production. When IL-4-/- Th2 cells are transferred into IL-4Ralpha-/- mice, mucus is not induced, and BAL eosinophilia is absent. These data suggest that in the absence of IL-4, IL-13 may be critical for Th2-induced mucus production and eosinophilia. To determine whether eosinophils are important in mucus production, IL-5-/- Th2 cells were transferred into IL-5-/- recipients. Eosinophilia was abolished, yet mucus staining in the epithelium persisted. These studies show definitively that IL-5, eosinophils, or mast cells are not essential, but signaling through IL-4Ralpha is critically important in Th2 cell stimulation of mucus production.
Cohn
L
L
Sections of Pulmonary and Critical Care Medicine and Immunobiology and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Homer
R J
RJ
MacLeod
H
H
Mohrs
M
M
Brombacher
F
F
Bottomly
K
K
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D053661:Interleukin-13 Receptor alpha1 Subunit; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D010047:Ovalbumin