Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma.
Eosinophils have been implicated as playing a major role in allergic airway responses. However, the importance of these cells to the development of this disease has remained ambiguous despite many studies, partly because of lack of appropriate model systems. In this study, using transgenic murine models, we more clearly delineate a role for eosinophils in asthma. We report that, in contrast to results obtained on a BALB/c background, eosinophil-deficient C57BL/6 Delta dblGATA mice (eosinophil-null mice via the Delta DblGATA1 mutation) have reduced airway hyperresponsiveness, and cytokine production of interleukin (IL)-4, -5, and -13 in ovalbumin-induced allergic airway inflammation. This was caused by reduced T cell recruitment into the lung, as these mouse lungs had reduced expression of CCL7/MCP-3, CC11/eotaxin-1, and CCL24/eotaxin-2. Transferring eosinophils into these eosinophil-deficient mice and, more importantly, delivery of CCL11/eotaxin-1 into the lung during the development of this disease rescued lung T cell infiltration and airway inflammation when delivered together with allergen. These studies indicate that on the C57BL/6 background, eosinophils are integral to the development of airway allergic responses by modulating chemokine and/or cytokine production in the lung, leading to T cell recruitment.
Walsh
Elizabeth Rose
ER
Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Sahu
Nisebita
N
Kearley
Jennifer
J
Benjamin
Ebony
E
Kang
Boo Hyon
BH
Humbles
Alison
A
August
Avery
A
D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D050982:GATA1 Transcription Factor / Q000172:deficiency / Q000235:genetics; D006967:Hypersensitivity / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D007378:Interleukins; D010047:Ovalbumin