Th2-mediated inflammatory signaling (Th2 signaling) (Th2 signaling)

Th2-mediated inflammatory signaling is a complex biological pathway characterized by the activation of T helper 2 (Th2) cells and the subsequent release of type 2 cytokines, primarily interleukin-4 (IL-4), IL-5, and IL-13 (Gandhi et al., 2016, Nature Reviews Drug Discovery). This pathway plays a critical role in the adaptive immune response against extracellular parasites but, when dysregulated, drives the pathogenesis of various allergic and atopic diseases such as asthma and atopic dermatitis (Gause et al., 2013, Nature Reviews Immunology). IL-4 and IL-13 signal through the IL-4 receptor alpha (IL-4Rα) to induce IgE class switching in B cells and promote tissue remodeling, while IL-5 is essential for the maturation and survival of eosinophils (UniProt P05113, P05112). Therapeutic intervention typically involves monoclonal antibodies like dupilumab or mepolizumab that neutralize these cytokines or block their receptors to dampen the chronic inflammatory response (FDA Label: Dupixent, Nucala). These therapies have revolutionized the management of chronic inflammatory conditions by providing targeted alternatives to broad-spectrum immunosuppressants like corticosteroids (Wenzel, 2012, Nature Medicine).

Other names

Type 2 inflammationTh2 immune responseT-helper 2 signalingAllergic inflammatory cascade

Drugs targeting this pathway typically function as monoclonal antibodies that neutralize specific type 2 cytokines (IL-4, IL-5, IL-13) or block their cognate receptors (IL-4Ra, IL-5Ra), thereby inhibiting downstream JAK-STAT signaling and reducing the recruitment and activation of inflammatory effector cells like eosinophils and mast cells (Gandhi et al., 2016).