Allergic asthma is a chronic airway inflammatory disease that is characterized by eosinophil infiltration, bronchial epithelium damage, and airway hyperreactivity (AHR), which result from pathogenic Th2-type immune responses to environmental allergens, such as house dust mites (HDM; Dermatophagoides sp.)[Nat Med 18:716-725 (2012)]. Hypersensitivity to HDM is one of the most common allergic responses [Curr Opin Allergy Clin Immunol 9:128-135 (2009)] and >50% of children and adolescents with asthma are sensitized to HDM. Although allergen-specific CD4+ Th2 cells orchestrate the HDM allergic response through their induction of IgE directed against mite allergens, activation of innate immune responses, such as by dendritic cells (DCs) in the airway mucosa, also plays a critical role in HDM-induced allergic inflammation [Allergy Asthma Immunol Res 5:68-74 (2013)].

We have investigated the effects of LTh(αK) in an allergic asthma murine model and its involvement in the maturation and function of DCs. Our results showed that intranasal administration of LTh(αK) or LTh(αK) in combination with HDM allergen, decreased AHR, and attenuated the cardinal features of allergen-induced airway inflammation. In addition, LTh(αK)/HDM also induced allergen specific IgA. These LTh(αK) effects may have resulted from modifying DCs functions to reverse allergic immune responses, as shown by our in vivo and in vitro results. Thus, a detoxified mutant form of LT, LTh(αK), may have clinical applications for allergy and asthma as an immune-modulator.

Treatment of allergy-Symptomatic treatment

  • ♦Currently the preferred treatment
  • ♦Attenuate symptoms with anti-histamines, steroid nasal sprays and anti-leukotrienes
  • ♦Most effective for patients with mild allergy symptoms
  • ♦No curative effect

 

Treatment of allergy-Immunotherapy treats the underlying cause of the allergy

  • ♦Immunotherapy with allergen
  • ♦Anti-IgE antibody (Xolair)
  • ♦Immune-modulator(CpG, CTB, LTh(αK))

 

  • LTh(αK) alleviated airway hyper-responsiveness, airway inflammation and mucus hyper-secretion in der p-induced asthma murine model.
  • •LTh(αK) pretreatment down regulated MHC class II expression of Der p-induced BMDCs from Der p-sensitized mice.

•LTh(αK) pretreatment inhibited IL-6 secretion of Der p or LPS-induced BMDCs from Der p-sensitized mice..