Abstract: The present invention relates generally to methods and compositions for reducing Interleukin-4 or Interleukin-13 signaling, in particular to treat asthma and atopic dermatitis. The inventors have found that Rac/PAK mediated endocytosis of the ligand bound type I (IL-4R with the chains IL-4Ra and IL-2-Rg) and/or type II receptor (IL-13R with the chains IL-4Ra and IL-13Ra1) is needed for the IL-4 and/or IL-13 mediated activation of downstream signalling events including phosphorylation of Stat family transcrition factors. These discoveries enable new methods of screening compounds that modulate Interleukin-4 and Interleukin-13 signalling, as well as new methods for treating conditions characterized by increased Interleukin-4 and Interleukin-13 levels. These conditions include inflammatory conditions, asthma bronchiale, atopic dermatitis, allergies, atopic syndromes, allergic rhinitis, and th2-induced conditions.