Thus, CpG motifs support development of regulatory T cells. 42 Accordingly, definitely they induced Th1 cells andor Tregs that inhibited Th2 immune responses and prevented allergen induced sensitization and airway inflammation in many animal models and clinical trials. At present, CpG motifs are more and more used as adjuvants for allergen specific immune therapy, even in humans. CpG motifs are conjugated with allergens. local or systemic administration of these conjugates generates allergen specific long lasting adaptive Th1 immune responses, induces Tregs, and probably also Inhibitors,Modulators,Libraries stimulates memory Th2 cells to shift into Th1 effector cells after further allergen contacts. 44 Lipopolysaccharides The so called farming effect belongs to the best described environmental factors that are associated with a diminished risk of atopic diseases.

45 It is based on intensive exposure to organic dust and thus to a variety of microbial antigens in stables on farms from early infancy on. Peters Inhibitors,Modulators,Libraries and colleagues recently confirmed protective properties of organic dust from stables with regard to allergen mediated sensitization and airway inflammation in a mouse model. 46 Several experimental Inhibitors,Modulators,Libraries studies in mice and humans have analyzed, in particular, the immuno modulatory allergy preventing effects of lipopolysacchar ides, the cell wall component of gram negative Inhibitors,Modulators,Libraries bacteria and an important ingredient of organic dust. In serum, LPSs bind their soluble receptors lipopolysacchar ide binding protein and CD14 and activate TLR 4. LBP and CD14 catalyze TLR 4 activation.

Inhibitors,Modulators,Libraries TLR 4 activation activates through the intracellular adaptor molecule MyD88 associated cytoplasmatic protein kinases such as IL 1 receptor associated kinase 4 and others, which leads to IkB phosphorylation and finally to NF kB activation. 34 Epidemiologic studies suggested that polymorphisms for CD14 and TLR 4 resulting in reduced responsiveness of DCs on LPSs are associated with an increased risk of developing atopic diseases. 47 In our own work in adult mice, local and systemic application of LPSs later suppressed allergen mediated sensitization and airway inflammation in an IL 12 dependent way. 48 In phase 3 neonatal mice, repetitive exposure to simple aerosolized LPSs did not prevent subsequent allergen sensitization, but in combination with allergen induced mucosal tolerance, LPSs elicited an unspecific Th1 immune response, which might diminish the susceptibility of organisms to a variety of environmental allergens. 49 Further, Wang and McCusker showed in a similar model that repetitive exposure of neonatal mice to LPS and ovalbumin led to development of tolerance inducing Tregs in later sensitized mice.