Interleukin-24 receptor (IL-24R)

The Interleukin-24 (IL-24) receptor is a multi-subunit complex belonging to the Type II cytokine receptor family. IL-24 signals through two distinct heterodimeric receptor complexes: IL-20R1/IL-20R2 (Type I) and IL-22R1/IL-20R2 (Type II). These receptors are primarily expressed on epithelial tissues, including the skin, lungs, and reproductive organs, as well as on various cancer cells. Upon ligand binding, the receptors activate the JAK/STAT signaling pathway, particularly STAT1 and STAT3, which regulates cell survival and immune responses. In oncology, IL-24 (also known as MDA-7) is notable for its ability to induce selective apoptosis in a wide range of cancer cells while sparing normal cells, a process often mediated by the induction of endoplasmic reticulum stress and reactive oxygen species. Consequently, therapeutic strategies have focused on delivering IL-24 via viral vectors or recombinant proteins to activate these receptors in tumors. Conversely, in chronic inflammatory diseases like psoriasis and rheumatoid arthritis, the overactivation of these receptors by IL-24 and related cytokines (IL-19, IL-20) contributes to tissue hyperplasia and inflammation, making the receptor subunits potential targets for antagonistic antibodies.

Other names

IL-20R1/IL-20R2 complexIL-22R1/IL-20R2 complexMDA-7 receptorMelanoma differentiation-associated gene 7 receptor

Agonism of the receptor complex via recombinant IL-24 or gene therapy (mda-7) triggers the JAK/STAT signaling pathway (primarily STAT1 and STAT3) and induces endoplasmic reticulum (ER) stress, leading to selective apoptosis in cancer cells. In inflammatory contexts, antagonism of the shared subunits (like IL-20R2) is explored to reduce cytokine-mediated tissue damage.