Interleukin‐4‐ and Interleukin‐13 receptors trigger distinct JAK/STAT activation patterns in mouse lymphocytes

Abstract Interleukin‐13 (IL‐13) is a T‐cell‐derived cytokine closely related to IL‐4 and functions as a central mediator of allergic asthma. The basis of overlapping activities of the two cytokines is the utilization of a common receptor subunit, the interleukin‐4 receptor α chain (IL‐4Rα). We addressed the signaling specificity of IL‐4 versus IL‐13, which rests on specific components of the respective receptor systems, i.e. the common γ chain (γc) for the IL‐4 receptor and the IL‐13 receptor α1 chain for the IL‐13 receptor. Hybrid receptors were engineered such that the consequences of intracellular pairing between IL‐4Rα and its two different dimerization partners could be directly compared in a background‐free fashion in mouse pro‐B cells. Experimentally induced dimers of both the IL‐4Rα/γc and the IL‐4Rα/IL‐13Rα1 type were capable of mediating a proliferative response and triggering STAT6 activity. Other JAK/STAT reactions, however, appeared characteristically distinct in the two systems. The IL‐4 receptor, upon activation, drove tyrosine phosphorylation of JAK1 and JAK3, whereas the IL‐13 receptor did not activate JAK3. Notably, only the IL‐4‐ but not the IL‐13 receptor was competent to evoke DNA‐binding activity of STAT5.