Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions

Abstract

Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHC-II. The expression of MHC-II on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance.Using an in vitro approach, NCR+ ILC3s generated from cord blood stem cell precursors were incubated under different O2 concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF-β1. The expression of MHC-II, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1% O2 reduced the expression of the MHC-II molecule HLA-DR as compared to 21% O2 and modulated the relative effects of hCG and TGF-β1.Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy.

IL17A Suppresses IGFBP1 in Human Endometrial Stromal Cells

“…In this study, decidualization of EnSCs isolated from the human endometrium and of the endometrial stromal cell line KC02-44D induced a significant upregulation of IL1B, IL23A, and IL17D expression [15,41], affecting the proliferation, differentiation, and functional regulation of γδ17T and ILC3 [30,33,[38][39][40]57,58], which is involved in innate immunity and embryo implantation in the endometrium. This finding prompted us to explore the interactions between decidualized EnSCs and IL17A-producing immune cells.…”

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

“…ILC3 is a small part of endometrial immune cells, which participate in innate defense mechanisms on mucous membranes (63). Uterine ILC3s play a preponderant role in embryo implantation and have an antimicrobial effect (64)(65)(66). Defects in ILC generation or functional interactions in decidual tissues may cause fetal loss (67).…”

IL-23 receptor signaling licenses group 3-like innate lymphoid cells to restrict a live-attenuated oral Chlamydia vaccine in the gut

“…It will be interesting to compare these IFNγ-susceptible mutants to determine whether they are all inhibited by the IL-23R signaling-dependent IFNγ + ILC3s in the colon. More importantly, the IL-23R signaling-dependent IFNγ + ILC3s pathway in the gut may also contribute to the oral chlamydia-induced transmucosal immunity in the genital tract since ILC3s can function as antigen presenting cells (74,(91)(92)(93) and ILC3sproduced IFNγ can drive Th1 phenotype (94). It will be important in testing the hypothesis that oral intrOv may use the IL-23R signaling pathway to induce IFNγ + ILC3s 17 in the gut for priming adaptive immunity via presenting chlamydial protective epitopes and promoting Th1 development in the genital tract.…”