Fig. 3

Model showing TAS2R-dependent modulation of progesterone (P4)’s role in protecting from pregnancy. P4 binds to TAS2Rs found in extravillous trophoblast (EVT) cells and enhances the release of progesterone-induced blocking factor (PIBF), perhaps via the canonical signalling cascade. This, subsequently binds to the PIBF receptor, which heterodimerises with the IL-4 receptor to activate the signal transducer and activator of transcription 6 (STAT6) transcription pathway for cytokine production by the type 2 T helper cells (Th2). On the type 1 T helper cells (Th1), PIBF acts to inhibit the STAT4 pathway by promoting interaction of suppressor of cytokine signalling 3 (SOCS-3) with the IL-12R receptor to attenuate Th1 cytokine production. Furthermore, PIBF inhibits the cytological activity (natural killer) of NK cells by blocking perforin and lytic enzyme degranulation. Finally, PIBF interacts with B cells, increasing the production of asymmetric antibodies. All this reduces cellular cytotoxicity and controls immunosuppression