Tregs traffiking during the decidualization and peri-implantation period

. L. GALLINO , E. GRASSO , V. HAUK, E. SOCZEWSKI , C. PEREZ LEIROS AND R. RAMHORST.

Mar del Plata

Congreso; Reunión anual conjunta de la Sociedad Argentina de Investigación Clínica y de la Sociedad Argentina de Inmunología; 2016

Decidualization process involves phenotype and functional changes on endometrial cells and the modulation of different mediators such as cytokines, chemokines and the selective recruitment of immune cells. The vasoactive intestinal peptide (VIP) is a neuropeptide produced by endometrial stromal cells involved in immunetolerance. Foxp3+ Tregs are needed for successful implantationbecause they prevent the development of a hostile uterine microenvironment.First, we determined the frequencies of CD4+Foxp3+ Tregs in female mice with reproductive fialures associated with VIP defficieny. We oberved by RT-PCR that in vivo, Foxp3 expression was not detectable in VIP-deficent mice uterus in contrast to wildtype mice samples from WT, VIP +/-, VIP -/- mice. After mating, females were checked daily for vaginal plugs. The day at which the vaginal plug was detected was considered day 0 of pregnancy. Animals were sacrificed at different pregnancy days and we perfomed determined foxp3 kinetic expression from 3.5 to 6.5. We observed a peak in foxp3 expression in uterus, mesenteric and inginal draning limph nodes at the implantation day 5.5. In fact using an in vitro model of human deidualization (Human endometrial stromal cell line (HESC) was treated or not with VIP or with medroxiprogesterone and dbcAMP), Decidualized cells selective recruit Foxp3+ cells, among monocytes and effector Tcells, associated with and increase CXCL12 expression. Taking into account that mucosal sites function together as a system-wide organ and VIP is an instestinal pepetide, we wonder if Tregs induction at the GALT were modulated during pregnancy. Therefore co-cultures between CACO cell line and maternal PBMCs were performed in presence of P4 (10-7M-10-8M), trophoblast conditioned media and VIP antagonist. P4 and conditioned media increased foxp3 expression while VIP antagonist prevent it, highlight VIP contribution. In conclusion, VIP may have an important role during decidualization contributing to control the immune micro-environment asociated with a selective recruitmet of maternal Tregs to the uterus.