Regulatory dendritic cells protect against allergic airway inflammation in a murine asthmatic model.
BACKGROUND
Dendritic cells (DCs) are crucial for the induction of immunity and tolerance. Despite an improved understanding of the DC-mediated control of T(H)1-biased immunity, little is known about how DCs regulate T(H)2-mediated immunity.


OBJECTIVE
The effects of immunostimulatory mature DCs (maDCs) and regulatory DCs (DCregs) on T(H)2-driven allergic immunity involving IgE production were examined.


METHODS
A murine model of airway hyperresponsiveness; the adoptive transfer of maDCs, DCregs, and T cells; and T-cell function were studied.


RESULTS
Antigen-pulsed maDCs inhibited antigen-specific IgE production but enhanced the production of antigen-specific IgG1 and IgG2a. Analysis of Ifng-/- mice and Il21r-/- mice revealed that the inhibitory effect of antigen-pulsed maDCs on antigen-specific IgE production involved IL-21-producing T follicular helper cells but not IFN-gamma-producing T(H)1 cells. In contrast, antigen-pulsed DCregs impaired the production of antigen-specific IgE, IgG1, and IgG2a. In vivo blockade experiments showed that antigen-specific CD4+CD25+Foxp3+ regulatory T cells mainly mediated the suppressive effect of antigen-pulsed DCregs on the production of antigen-specific IgE. Antigen-pulsed maDCs promoted airway inflammation, whereas antigen-pulsed DCregs markedly suppressed the pathogenesis.


CONCLUSIONS
DCregs abolish T(H)2-mediated IgE production and allergic inflammation based on antigen-specific dominant tolerance, whereas maDCs exacerbate the pathogenesis despite inhibiting the IgE response through the activation of diverse types of T(H) cell responses.
Fujita
Shigeharu
S
Laboratory for Dendritic Cell Immunobiology, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
Yamashita
Naomi
N
Ishii
Yasuyuki
Y
Sato
Yumiko
Y
Sato
Kaori
K
Eizumi
Kawori
K
Fukaya
Tomohiro
T
Nozawa
Risa
R
Takamoto
Yukiko
Y
Yamashita
Naohide
N
Taniguchi
Masaru
M
Sato
Katsuaki
K
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory