T-helper cell type 2-mediated signaling pathway (Th2 pathway)

The T-helper cell type 2 (Th2)-related pathway, also known as Type 2 inflammation, is a complex signaling network primarily driven by cytokines such as Interleukin-4 (IL-4), Interleukin-5 (IL-5), and Interleukin-13 (IL-13) (Gandhi et al., 2016, Nature Reviews Drug Discovery). These cytokines are produced by Th2 cells and innate lymphoid cells (ILC2s) to coordinate immune responses against parasites, but their dysregulation leads to allergic diseases (Fahy, 2015, Nature Reviews Immunology). IL-4 and IL-13 share the IL-4 receptor alpha (IL-4Rα) subunit, which triggers STAT6 signaling to promote IgE production and airway hyperresponsiveness (Wenzel, 2012, Nature Medicine). IL-5 is specifically responsible for the maturation, recruitment, and survival of eosinophils, a hallmark of eosinophilic asthma (Varricchi et al., 2016, Frontiers in Immunology). Therapeutic intervention involves biologics like Dupilumab, which blocks IL-4Rα, or Mepolizumab, which neutralizes IL-5, thereby reducing the inflammatory burden in patients with Type 2-high endotypes (Castro et al., 2018, New England Journal of Medicine). Monitoring biomarkers such as blood eosinophils and fractional exhaled nitric oxide (FeNO) is essential for identifying patients most likely to benefit from these targeted therapies (Corren et al., 2011, New England Journal of Medicine).

Other names

Type 2 inflammationTh2 immune responseIL-4/IL-5/IL-13 signaling axisType 2 cytokine signaling

Monoclonal antibodies target and neutralize specific Th2 cytokines (IL-4, IL-5, IL-13, TSLP) or their respective receptors (IL-4Rα, IL-5Rα) to inhibit downstream signaling cascades and reduce type 2 inflammation.