Molecular definition of group 1 innate lymphoid cells in the mouse uterus

Abstract

Determining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-β, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.

Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy

“…There are three murine Group 1 ILC subsets: CD49a+Eomes-uterine ILC1 (uILC1), CD49a+Eomes +trNK and CD49a-Eomes+conventional NK (cNK) 4,46,47 . Murine uILC1 express CXCR6 and may represent memory cells as they expand in second pregnancies 46 . They therefore could be functionally analogous to KIR+PTdNK, although they have low levels of Ly49.…”

Differentiation of c‐Kit + CD24 + natural killer cells into myeloid cells in a GATA‐2‐dependent manner

“…57 When heterogeneity of c-Kit + CD24 + NK cells were assessed through tSNE analysis of flow cytometry data, c-Kit + CD24 + NK cells were a quite homogeneous cell population in expression of NK cell markers. Although some of c-Kit + CD24 + NK cells dimly expressed several myeloid cell markers, it has previously been reported that NK cells express several myeloid cell markers, [57][58][59][60][61][62] suggesting that c-Kit + CD24 + NK cells are a homogeneous NK cell population with heterogeneity of several myeloid cell markers. To further investigate these issues of identity and heterogeneity of c-Kit + CD24 + NK cells, high dimensional single-cell analysis such as single-cell RNA sequencing or mass cytometry will be required.…”

NK cells induce hepatic ER stress to promote insulin resistance in obesity through osteopontin production

“…17,20 The alymphoid Rag2 −/− Il2rg −/− mice dams express less Spp1, indicating lymphocytes are an important source of OPN. 35 Activated Kupffer cells contribute to hepatic IR in obese mice. 36 Kupffer cells and macrophage-derived OPN, and the subsequent effect of OPN on these cells in the liver warrant further attention in future studies.…”