T-helper type 2 pathway cytokine receptors

The T-helper type 2 (Th2) pathway cytokine receptors are a group of transmembrane proteins that mediate the signaling of cytokines central to type 2 inflammation, primarily interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) (Gandhi et al., 2016). These receptors, including the interleukin-4 receptor alpha (IL-4Rα) and the interleukin-5 receptor alpha (IL-5Rα), are expressed on various immune and structural cells, where they activate the JAK-STAT signaling pathway to drive processes such as IgE production, eosinophil recruitment, and mucus hypersecretion (Gandini et al., 2022). Pathological overactivation of these receptors is a defining feature of "Th2-high" diseases, including severe allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps (Wenzel, 2012). Therapeutic agents such as dupilumab (targeting IL-4Rα) and benralizumab (targeting IL-5Rα) have been developed to specifically inhibit these receptors or their ligands, providing significant clinical benefit for patients with refractory type 2 inflammation (Kariyawasam et al., 2023). Monitoring biomarkers like blood eosinophil counts and fractional exhaled nitric oxide (FeNO) is essential for identifying patients most likely to respond to these targeted therapies (Couillard et al., 2021).

Other names

Th2 cytokine receptorsType 2 cytokine receptorsInterleukin-4/5/13 receptorsTh2 pathway receptors

Inhibition of type 2 cytokine signaling by either blocking specific receptor subunits (e.g., IL-4Rα, IL-5Rα) or neutralizing the ligand cytokines (IL-4, IL-5, IL-13) to prevent receptor activation and downstream JAK-STAT signaling.