Abstract
We previously showed that although systemic administration of alpha-galactosylceramide (alphaGalCer) or agonistic anti-CD40 induced functional maturation of dendritic cells (DC) in mesenteric lymph nodes, only the former treatment succeeded in breaking the induction of oral tolerance. In this study, we looked for the essential factor responsible for the disruption of oral tolerance. We found that lamina propria (LP)-DC was responsible for the oral OVA presentation and that Peyer's patch was not essential for the induction of oral tolerance. Therefore, we investigated the role of LP-DC. Treatment with alphaGalCer but not with anti-CD40 induced the full maturation of LP-DC at an early time point. This functional activation of LP-DC was mediated by strong activation of NKT cells that reside abundantly in the small intestinal lamina propria (SI-LP) and interferon-gamma partially contributed to the LP-DC activation. LP-DC isolated from alphaGalCer-treated OVA-fed mice induced the differentiation of naïve CD4+ T cells into Th1 and Th2 and was associated with the reduced Foxp3+ population. In contrast, LP-DC isolated from anti-CD40-treated OVA-fed mice failed to generate Th cell differentiation but induced more Foxp3+ CD4+ T cells. Our results demonstrate that triggered by NKT cells in SI-LP, functional maturation of Ag-capturing DC from SI-LP is necessary for the abrogation of oral tolerance induction.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
