Acetylcholine polarizes dendritic cells toward a Th2-promoting profile

GORI S,; VERMEULEN M,; REMES-LENICOV F, ; JANCIC C, ; SCORDO W, ; CEBALLOS A, ; TOWSTYKA N,; BESTACH Y,; BELLI C, ; SABBIONE F; GEFFNER J, ; SALAMONE G.

ALLERGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2017

0105-4538

BACKGROUND:Maternal antigen-presenting cells attracted to the pregnant uterus interact with trophoblast cells and modulate their functional profile to favour immunosuppressant responses. Non-neuronal cholinergic system is expressed in human cytotrophoblast cells and in immune cells with homeostatic regulatory functions.AIM:The aim of this work was to evaluate whether non-neuronal acetylcholine conditions maternal monocyte and DC migration and activation profiles.METHODS:We used an in vitro model resembling maternal-placental interface represented by the co-culture of human trophoblast cells (Swan-71 cell line) and monocytes or DC.RESULTS:When cytotrophoblast cells were treated with neostigmine (Neo) to concentrate endogenous acetylcholine levels, monocyte migration was increased. In parallel, high levels of IL-10 and decreased levels of TNF-á were observed upon interaction of maternal monocytes with trophoblast cells. This effect was synergized by Neo and was prevented by atropine, a muscarinic acetylcholine receptor antagonist. Similarly, trophoblast cells increased the migration of DC independently of Neo treatment; however, enhanced IL-10 and MCP-1 synthesis in trophoblast-DC co-cultures with no changes in TNF-á and IL-6 was observed. In fact, there were no changes in HLA-DR, CD86 or CD83 expression. Finally, trophoblast cells treated with Neo increased the expression of two antigen-presenting cells attracting chemokines, MCP-1, MIP-1á and RANTES through muscarinic receptors, and it was prevented by atropine.CONCLUSIONS:Our present results support a novel role of acetylcholine synthesized by trophoblast cells to modulate antigen-presenting cell migration and activation favouring an immunosuppressant profile that contributes to immune homeostasis maintenance at the maternal-foetal interface.