Vasoactive intestinal peptide production by human first trimester trophoblast cells induces a tolerogenic microenvironment

FRACCAROLI L; GRASSO E; HAUK V; MOR G; PÉREZ LEIRÓS C; RAMHORST R

Los Cocos, Córdoba

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2013

Embryo implantation requires an initial inflammatory response that must be regulated towards a tolerogenic one. For this, iTreg cells are essential for tolerance induction during this transition period. Vasoactive intestinal peptide (VIP) promotes anti-inflammatory and immunosuppressive profiles in immune cells through its specific receptors VPAC1 y VPAC2. In the present work we evaluated the contribution of trophoblast cells producing VIP to the generation of a tolerogenic signature, with focus on the induction of maternal Treg cells. To evaluate this, we developed an in vitro model of maternal leukocytes and trophoblast cells interaction represented by co-cultures of fertile women PBMCs and trophoblast cell lines from first trimester (Swan-71) or third trimester (JEG-3 and BeWo). Swan-71 cells express and secrete VIP, evaluated by PCR and ELISA, and its receptor VPAC1 (qRTPCR). VIP (10-7M) increased the frequency of CD4+CD25+Foxp3+ cells after 48h of co-culture with Swan-71 (3.9±0.4% vs 8.3±0.6%, p