Functional maturation of lamina propria dendritic cells by activation of NKT cells mediates the abrogation of oral tolerance.
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.
Chang
Jae-Hoon
JH
Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, Korea.
Lee
Jung-Mi
JM
Youn
Hyun-Jun
HJ
Lee
Kyoo-A
KA
Chung
Yeonseok
Y
Lee
Ah-Young
AY
Kweon
Mi-Na
MN
Kim
Ho-Youn
HY
Taniguchi
Masaru
M
Kang
Chang-Yuil
CY
D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology; D055785:Gene Knockdown Techniques; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma; D010047:Ovalbumin