Expression of the Ym2 lectin-binding protein is dependent on interleukin (IL)-4 and IL-13 signal transduction - Identification of a novel allergy-associated protein

Asthma pathophysiology is intimately regulated by CD4(+) Th2 lymphocytes an d the cytokines interleukin (IL)-4 and IL-13. However, the mechanisms by wh ich these cytokines promote disease have not been fully elucidated. In orde r to identify novel molecular mediators of allergy, a comparison was made o f the bronchoalveolar lavage, which demonstrated that the Ym2 protein was a bundantly up-regulated in the lung during the development of allergy. Low l evels of the Ym1 isomer were also detected. Importantly, neither Ym1 nor Ym 2 has been characterized previously in the context of allergic pulmonary in flammation. Western immunoblot showed that enhanced expression of these pro teins was dependent on CD4(+) T cells and IL-4 or IL-13 signaling via the I L-4R alpha subunit. In addition, intratracheal instillation of IL-13 into n aive mice was sufficient to induce expression. Ym1 is homologous to eosinop hil chemotactic factor L. However, only weak eosinophil chemotaxis was obse rved in response to Ym protein in both in vitro and in vivo assays. By cont rast, the homology of Ym1 and Ym2 to proteins associated with tissue remode ling, together with the previous findings that Ym1 is homologous to chitina se and binds heparin sulfate and GlcN oligomers (chitobiose, chitotriose, a nd chitotetraose), strongly suggests these proteins play an important role in airway wall remodeling in the allergic lung.