Deciphering the Receptor-Mediated Signaling Pathways of Interleukin-19 and Interleukin-20.

Interleukin-19 (IL-19) and Interleukin-20 (IL-20) are inflammatory cytokines belonging to the IL-10 family with immunoregulatory properties. Emerging evidence highlights the importance of association of these cytokines with both immunological and inflammatory disorders, including chronic inflammation, cardiac dysfunction, and cancer. IL-19 and IL-20 bind to the heterodimeric receptor complex and induce multiple downstream signaling cascades by activating the signal transducer and activator of transcription 3 (STAT3), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT1), and NFKB inhibitor alpha (NFKBIA), leading to proinflammatory and anti-inflammatory reactions in cancer, inflammation, tumor microenvironment, and infectious diseases. Considering the significant role of these cytokines, we integrated its cellular signaling network by combining multiomics molecular events associated with 56 molecules of induced by IL-19 and 156 molecules of by IL-20. The reactions of these signaling events are classified into enzyme catalysis/post-translational modifications, activation/inhibition events, molecular associations, gene regulations at the mRNA and protein level, and the protein translocation events. We believe that this signaling pathway map would serve as a knowledge base, that aid researchers and clinicians to understand and explore the intricate mechanisms and identify novel signaling components and therapeutic targets for diseases associated with dysregulated IL-19 and IL-20 signaling.