Lipopolysaccharides modulate allergen-specific immune regulation in a murine model of mucosal tolerance induction.

Farming has been widely reported to be associated with decreased risk of developing atopic disorders, but underlying immunomodulatory mechanisms are still not fully defined. We delineated T-cell functions after induction of mucosal tolerance in the context of intranasally delivered organic dust compounds, lipopolysaccharides (LPS). BALB/c mice were pretreated intranasally with ovalbumin (OVA) with or without LPS (Escherichia coli) three times (days -21, -14, -7) prior to systemic OVA sensitization (days 1 and 14) and airway allergen challenges (days 28-30). CD4+ spleen T cells from pretreated and sensitized donors were characterized for cytokine function, and transferred into naive recipients prior to subsequent OVA sensitization and challenges. Intranasal OVA pretreatment suppressed Th2-mediated immune and inflammatory responses and enhanced frequency of regulatory T cells in OVA-sensitized and -challenged mice. Addition of LPS to OVA, but not LPS alone, inhibited development of allergen-induced sensitization and eosinophilic airway infiltration, and markedly enhanced allergen-specific IgG1 serum levels and frequencies of IL-10- and IFN-gamma-producing CD4+ T cells. Transfer of CD4+ spleen T cells from OVA-pretreated animals protected naive recipients against subsequent allergen sensitization and airway disease, whereas transfer from LPS/OVA-pretreated animals only protected against allergen sensitization. Microbial LPS modulated mucosal tolerance by inducing allergen-specific IgG1 production and distinct effector CD4+ T cells with a mixed regulatory/Th1 phenotype. Organic dust components such as LPS might therefore be important immune modulators in naturally occurring or preventive allergen-specific tolerance induction.

Gerhold K ，Avagyan A ，Reichert E ，Blumchen K ，Wahn U ，Hamelmann E ... -  《-》

4-1 BB stimulation inhibits allergen-specific immunoglobulin E production and airway hyper-reactivity but partially suppresses bronchial eosinophilic inflammation in a mouse asthma model.

Cho YS ，Kwon B ，Lee TH ，Kim TB ，Moon KA ，La S ，Lee J ，Lee SD ，Oh YM ，Moon HB ... -  《CLINICAL AND EXPERIMENTAL ALLERGY》

Toll-like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin-specific allergic airway disease: role of MyD88 adaptor molecule and interleukin-12/interferon-gamma axis.

Bortolatto J ，Borducchi E ，Rodriguez D ，Keller AC ，Faquim-Mauro E ，Bortoluci KR ，Mucida D ，Gomes E ，Christ A ，Schnyder-Candrian S ，Schnyder B ，Ryffel B ，Russo M ... -  《-》

Prenatal initiation of endotoxin airway exposure prevents subsequent allergen-induced sensitization and airway inflammation in mice.

Gerhold K ，Avagyan A ，Seib C ，Frei R ，Steinle J ，Ahrens B ，Dittrich AM ，Blumchen K ，Lauener R ，Hamelmann E ... -  《JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY》

Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323-339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance.

Barbey C ，Donatelli-Dufour N ，Batard P ，Corradin G ，Spertini F ... -  《CLINICAL AND EXPERIMENTAL ALLERGY》