This cytokine is the principal driver of type 2 immunity and the defining differentiation signal for the Th2 lineage. IL-4 is produced by activated Th2 cells, mast cells, basophils, eosinophils and ILC2s, and acts on both lymphoid and non-lymphoid targets.
In B cells it induces class switch recombination to IgE and IgG4 and upregulates MHC class II and CD23; in naive CD4+ T cells it drives Th2 commitment through STAT6 and GATA3 while suppressing Th1 and Th17 programmes; and in monocytes and macrophages it is the canonical polarising signal for the alternatively activated (M2) phenotype, inducing arginase-1, MRC1/CD206 and CD163. It is also mitogenic for activated T cells and a widely used component of media for M2 macrophage polarisation and dendritic cell differentiation. Signalling upregulates transcriptional programmes governing (i) Th2 lineage commitment via STAT6 and GATA3, (ii) survival and proliferation via IRS-2 and PI3K/AKT, (iii) immunoglobulin class switching via AID induction, and (iv) alternative macrophage activation via STAT6 and PPARg. The protein adopts a left-handed antiparallel four-helix bundle with up-up-down-down topology, stabilised by three intrachain disulfide bonds.
