Lineage-specific IKKβ deficiency reveals a role for intestinal epithelial cells in lung immune response to ingested antigens (163.10)

Abstract

Abstract The sites where immune responses are initiated are believed to play a key role at shaping subsequent responses at distant mucosal sites. However, little is known about the relative contribution of intestinal epithelial cells (IEC) to lung reactivity to foreign antigens and the development of allergic and non-allergic asthma. It has been demonstrated that nuclear factor κB (NF-κB) activation by IκB kinase (IKK)β deletion in macrophages increases pro-inflammatory cytokines responses. To address the potential regulatory effect of IEC for lung reactivity, control C57BL/6 mice and mice deficient in IKKβ in IEC (IKKβΔIEC) or in macrophage (IKKβΔMac) were orally sensitized by administration of ovalbumin and cholera toxin as adjuvant. All groups developed similar levels of antigen-specific IgE responses, but IgG2a responses were enhanced in IKKβΔIEC and, even more in IKKβΔMac. Subsequent nasal challenges of C57BL/6 mice with ovalbumin induced lung inflammation and increased lung resistance. Interestingly, both lung inflammation and lung resistance were lower in IKKβΔIEC mice and further reduced in IKKβΔMac mice. Taken together, these results show that localized alteration of NF-κB signaling in IECs have broader effects on immune responses to ingested antigen, which were similar, although of lower magnitude, than those seen when NF-κB signaling is altered on macrophages. They also reveal that IECs can shape immune responses at distant mucosal sites of the airways.