Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI-3) prevent airway hyper-responsiveness in experimental asthma.

Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3–/– mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1+ cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c+ cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD11c+ cells isolated from EBI-3–/– mice express markers of a more plasmacytoid phenotype without releasing IFN-α as compared to those from wild-type littermates. Moreover, allergen challenge induced the development of myeloid CD11c+ cells in the lungs of EBI-3–/– mice, which released increased amounts of IL-10 and IL-12 while not expressing IFN-α. Finally, inhibition of EBI-3 expression in lung DC could prevent AHR in adoptive transfer studies by suppressing mediator release of effector cells into the airways. These results indicate a novel role for EBI-3 in controlling local immune responses in the lungs in experimental asthma.