EBI3 deficiency leads to diminished T helper type 1 and increased T helper type 2 mediated airway inflammation
Despite extensive investigation of the signals required for development of T helper type 1 (Th1) and type 2 (Th2) immune responses, the mechanisms involved are still not well-defined. A critical role for Epstein–Barr virus-induced gene 3 (EBI3) in these responses has been proposed. EBI3, initially discovered as a transcriptionally activated gene in Epstein–Barr virus-infected B lymphocytes, codes for a subunit of the cytokine interleukin-27 (IL-27). While initial studies suggested that it had an important role in promoting Th1 responses, subsequent studies have revealed that EBI3 receptor signalling influences a variety of immune cell types and can inhibit both Th1 and Th2 responses. In the present study, we evaluated EBI3−/− mice for their ability to mount both Th1-mediated and Th2-mediated airway inflammatory responses. The EBI3−/− mice sensitized by exposure to inhaled ovalbumin plus a high dose of lipopolysaccharide, which normally results in Th1 responses in wild-type (WT) mice, instead developed Th2 type airway inflammation, with increased numbers of eosinophils. The EBI3−/− mice that were exposed to inhaled ovalbumin with a low dose of lipopolysaccharide, which induces Th2 responses in WT mice, showed a marked enhancement of these responses, with increased airway eosinophils, increased serum IgE levels and increased levels of Th2 cytokines (IL-4, IL-5 and IL-13) in culture supernatants of mediastinal lymph node cells. Increased production of Th2 cytokines was also seen when naive CD4+ T cells from EBI3−/− mice were stimulated in vitro compared with cells from WT mice. These results provide the first evidence that EBI3 may play an inhibitory role in allergic asthma development.
Document Type: Research Article
Affiliations: 1: Department of Pediatrics, Section of Pediatric Pulmonology, Yale University School of Medicine, New Haven, CT 2: Department of Dermatology, Yale University School of Medicine, New Haven, CT 3: President’s Office, Wellesley College, Wellesley, MA, USA
Publication date: April 1, 2011