Resident effector memory Tregs of the uterus regulate trophic functions during mouse early pregnancy. Resident effector memory Tregs of the uterus regulate trophic functions during mouse early pregnancy

Regulatory T cells (Tregs) contribute to successful pregnancy by promoting maternal-fetal tolerance. We identified a novel population of CD25-Foxp3+ resident uterine Tregs in non-pregnant mouse uterus. They have phenotypic and migration properties of tissue-resident effector-memory T cells (Trm), thus identifying regulatory Trm (regTrm). Lack of CD25 expression in regTrm is caused by the IL-2-deprived uterine microenvironment. We performed a complete transcriptome analysis by RNA-seq to determined whether uterine regTrm have a unique molecular signature, as has been described for other tissue Tregs. For this, we purified CD25- regTrm from non-pregnant and pregnant uterus at day 6 to 8 of pregnancy, and we compared them to CD4+Foxp3- (CD4conv) T cells from non-pregnant uterus and to CD25+ Tregs from paraaortic uterine draining lymph nodes. We used criteria of (i) a two-fold or greater change in expression and (ii) a p-value mice at day 6 to 8 of pregnancy, and from paraaortic lymph nodes of non-pregnant mice. Data were generated by RNA sequencing, in quadruplicate, using Illumina NextSeq.