IL12A

IL12A, also known as interleukin-12 alpha chain or p35, is a human gene that encodes the p35 subunit of the heterodimeric cytokine interleukin-12 (IL-12). The p35 subunit is paired with the p40 subunit (IL12B) to form bioactive IL-12. The p35 subunit alone is not secreted; assembly with p40 is required for cytokine activity and secretion by activated antigen-presenting cells such as dendritic cells and macrophages.

In the IL-12 cytokine, the p35 and p40 subunits create a heterodimer that signals through a receptor composed of IL-12Rβ1 and IL-12Rβ2. This triggers JAK-STAT signaling, particularly STAT4, promoting differentiation of naive CD4+ T cells into Th1 cells and inducing production of interferon-gamma by natural killer and T cells, thereby supporting cell-mediated immunity.

IL12A also contributes to the formation of IL-35, a different immunoregulatory cytokine formed by p35 and EBI3. IL-35 is produced by regulatory T cells and regulatory B cells and has immunosuppressive properties in some contexts.

Expression of IL12A is regulated by inflammatory stimuli such as toll-like receptor activation and cytokines like IFN-γ. Transcriptional and post-transcriptional regulation influences tissue-specific expression patterns. Genetic variation and altered expression of IL12A have been explored in autoimmune diseases and infectious diseases, and components of the IL-12 signaling axis are targets for immunomodulatory therapies, including antibodies targeting IL-12/IL-23p40.