title: Death receptor-6 regulates the development of pulmonary eosinophilia and airway inflammation in a mouse model of asthma.
abstract: Death receptor-6 (DR6), a member of the death domain-containing TNFR superfamily, is highly expressed in lymphoid tissues and regulated upon lymphocyte activation. Targeted disruption of DR6 results in enhanced CD4(+) T cell proliferation and T helper 2 (Th2) differentiation in vitro, whereas the in vivo role of DR6 in regulating Th2 cell differentiation and effector function remains largely unknown. In the current study, we used a Th2-skewed allergic airway inflammation model induced by ovalbumin (OVA) sensitization and challenge to compare the inflammatory response in the lung of both wild type (WT) and DR6(-/-) mice. DR6(-/-) mice were protected from the development of airway inflammation as evidenced by attenuated eosinophil accumulation and reduced mucus-producing cells in the lining airways of allergen-challenged animals. Consistent with these observations, a profound reduction of Th2 cytokine production (IL-5 and IL-13) was detected in the bronchoalveolar lavage fluid (BAL). Furthermore, a significant increase in the frequency of IFN-gamma secreting cells was observed in the DR6(-/-) mouse lungs after OVA challenge, which may account for the reduced pulmonary Th2 cytokine production. These data point to a critical role of DR6 in regulating airway inflammation in the OVA-induced mouse model of asthma.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. venkataramanch@lilly.com
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Venkataraman
authors.forename: Kathleen
authors.initials: K
authors.lastname: Justen
authors.forename: Jingyong
authors.initials: J
authors.lastname: Zhao
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Galbreath
authors.forename: Songqing
authors.initials: S
authors.lastname: Na
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; C485251:Tnfrsf21 protein, mouse; D007371:Interferon-gamma; D010047:Ovalbumin