IL4

Interleukin-4 (IL-4) is a cytokine in the interleukin-4 family that plays a central role in orchestrating humoral and cellular immune responses. It is produced by activated CD4+ Th2 cells, as well as by basophils, mast cells, and eosinophils, and it influences B cells and other immune cell types. In B cells, IL-4 promotes proliferation and differentiation and drives class switch recombination toward IgE in humans (and IgG1 in mice), linking it to allergic responses.

Mechanism and signaling: IL-4 signals through two major receptor configurations. The Type I receptor comprises IL-4Rα and the common γ chain (γc) and is primarily on hematopoietic cells, while the Type II receptor comprises IL-4Rα and IL-13Rα1 and can be engaged by both IL-4 and IL-13. Signaling involves JAK kinases (JAK1, JAK3, TYK2) and activation of the transcription factor STAT6, which drives gene expression programs that shape the immune response.

Biological roles: IL-4 promotes the differentiation of naive T cells toward a Th2 phenotype, supports alternative activation of macrophages (M2), and enhances mucus production and tissue remodeling. It also modulates dendritic cell function and helps regulate antibody production, reinforcing humoral immunity while suppressing Th1-mediated responses. IL-4’s activities are important for defense against helminth infections but contribute to allergic inflammation when dysregulated.

Clinical relevance: Elevated IL-4 signaling is associated with allergic diseases such as atopy, rhinitis, and asthma. Therapies targeting the IL-4/IL-13 axis, including anti-IL-4Rα antibodies like dupilumab, inhibit signaling from both cytokines and are used to treat several allergic and inflammatory conditions.

Classification: IL-4 is a member of the four-helix bundle cytokine family and shares receptor components and functions with IL-13, reflecting overlapping roles in immune regulation.