Aside from expected evidence that inhibition of interleukin-13 and interleukin-4 impaired host responses to helminth infections, we did not identify other preclinical evidence suggesting safety risks relating to infection, malignancy or cardiovascular events.
The intestinal response to helminth infection is mediated by a recently established type 2 immune circuit that consists of intestinal tuft cells and type 2 innate lymphoid cells (ILC2s).Schneider et al. have discovered that tuft cells sense succinate fermented by Tritrichomonas via GPR91 to drive the IL-25-ILC2-IL-13-dependent immune circuit and intestinal remodeling.
The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have important roles in stimulating innate and adaptive immune responses that are required for resistance to helminth infection, promotion of allergic inflammation, metabolic homeostasis and tissue repair.
Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases.
IL-13 is a signature cytokine of the helper T cell type 2 (TH2) pathway which underlies host defense to helminthic infection and activates production of IgE in both parasitized populations and in urban settings after allergen exposure.
Although well studied in settings of helminth infection and allergen sensitization, the combined contributions of IL-4 and IL-13 and their signaling pathways in models of viral pathogenesis have not been reported.
Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases.