The Immunobiology of Prostanoid Receptor Signaling in Connecting Innate and Adaptive Immunity
Figure 1
PGE2 and PGD2 receptor signaling in the bidirectional activating crosstalk between DCs and NK cells in normal and pathological conditions. (a) NK cells can interact with DCs through a range of cell surface receptors and production of various molecules both in the periphery and the secondary lymphoid organs. Activated immature DCs produce various cytokines, such as IL-12 that could act on NK cells recruited from the periphery by inflammatory signals and/or DC-derived chemokines. They induce NK-cell survival, proliferation, cytokine production, activation, and cytotoxicity. In turn activated NK cells produce cytokines, especially TNFα, which induces DC maturation process. When produced by DCs, PGE2 could inhibit NK cell activation through an EP2/EP4 receptor-dependent mechanism. Thus, inhibited NK cells could not stimulate DC maturation and function. The endogenously produced PGE2 can also reduce DC function in an autocrine manner via EP2/EP4 receptor subtypes. The tumor cells and stroma cells release diverse immunosuppressive agents, such as PGE2, which inhibits DC biology and NK effector functions through EP2 and/or EP4 receptor signaling. Tumor infiltrating DCs contribute also to increased levels of PGE2, which inhibits NK and DC functions and their crosstalk. (b) PGD2 produced by DCs or by mast cells has both autocrine and paracrine effects on DCs and NK cells through EP2 and/or EP4 receptors.
