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

Abstract

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-a as compared to those from wildtype 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-a. 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.

Immunosurveillance of Lung Melanoma Metastasis in EBI-3-Deficient Mice Mediated by CD8+ T Cells

“…In fact, T-bet-deficient mice have increased metastases load accompanied by reduced number of NK cells and no NKT cells infiltrating tumor-bearing tissue in this model, thus providing an appropriate genetic background on the role of NK cells in EBI-3-deficient mice (14). Consistently, we previously reported increased T-bet in the lung of EBI-3 −/− mice in a murine model of asthma (18). Taken together, these results suggest a role of T-bet in EBI-3 −/− -mediated melanoma protection, confirming a role of IFN- γ in our findings and providing a linkage between innate and adaptive immune-response in tumor.…”

“…The CD11c + and CD8 + lung cells were directly purified from isolated lung cell suspension according to the manufacturer’s instructions and as previously described (18, 19). After three washes in complete medium, the CD11c + cells were cultured with LPS ( Escherichia coli 0111:B4 LPS, 1 μ g/ml; InvivoGen) for 24 h at a density of 10 6 cells/ml.…”

Dual Role of Interleukin-1α in Delayed-Type Hypersensitivity and Airway Hyperresponsiveness

“…To assess airway hyperresponsiveness (AHR), we used an invasive whole-body plethysmograph as described previously [18]. Anesthetized mice were allowed to breathe spontaneously through intratracheal catheters (Mouse Ventilator, Ugo Basile).…”

Cutting Edge: A Key Pathogenic Role of IL-27 in T Cell- Mediated Hepatitis

“…IL-27 may exert both pro-and anti-inflammatory functions (5,6). It can augment T cell proliferation and enhance synthesis of IFN-␥ through the induction of T-bet and the activation of STAT-4 (1).…”