Interleukin-35 (IL-35) uses a unique Signal transducer and activator of transcription 1-alpha/beta - Signal transducer and activator of transcription 4 (STAT1:STAT4) heterodimer (Collinson et al. 2012) for signaling. Several cytokine receptors activate STAT1 and STAT4 to drive proinflammatory T helper 1 type responses, so it is unclear how their activation via the interleukin-35 receptor gives rise to a unique STAT dimer.
T cells stimulated with Interleukin-12 plus IFN-gamma (IFNG) induce minimal interaction of a STAT1:STAT4 with consensus STAT-binding sites in the IL12A and EBI3 promoters. However, T cells stimulated with Interleukin-35 showed considerable enrichment for the binding of STAT1 and STAT4 to IL12A position 250 and EBI3 position 500, as well as other sites in their promoters.
This reaction is presented as a black box because the exact mechanism of traslocation to the nucleus is unclear.