Emerging Concepts in Innate Lymphoid Cells, Memory, and Reproduction

Abstract

Members of the innate immune system, innate lymphoid cells (ILCs), encompass five major populations (Natural Killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells) whose functions include defense against pathogens, surveillance of tumorigenesis, and regulation of tissue homeostasis and remodeling. ILCs are present in the uterine environment of humans and mice and are dynamically regulated during the reproductive cycle and pregnancy. These cells have been repurposed to support pregnancy promoting maternal immune tolerance and placental development. To accomplish their tasks, immune cells employ several cellular and molecular mechanisms. They have the capacity to remember a previously encountered antigen and mount a more effective response to succeeding events. Memory responses are not an exclusive feature of the adaptive immune system, but also occur in innate immune cells. Innate immune memory has already been demonstrated in monocytes/macrophages, neutrophils, dendritic cells, and ILCs. A population of decidual NK cells characterized by elevated expression of NKG2C and LILRB1 as well as a distinctive transcriptional and epigenetic profile was found to expand during subsequent pregnancies in humans. These cells secrete high amounts of interferon-γ and vascular endothelial growth factor likely favoring placentation. Similarly, uterine ILC1s in mice upregulate CXCR6 and expand in second pregnancies. These data provide evidence on the development of immunological memory of pregnancy. In this article, the characteristics, functions, and localization of ILCs are reviewed, emphasizing available data on the uterine environment. Following, the concept of innate immune memory and its mechanisms, which include epigenetic changes and metabolic rewiring, are presented. Finally, the emerging role of innate immune memory on reproduction is discussed. Advances in the comprehension of ILC functions and innate immune memory may contribute to uncovering the immunological mechanisms underlying female fertility/infertility, placental development, and distinct outcomes in second pregnancies related to higher birth weight and lower incidence of complications.

Protection conferred by intraperitoneal Group AStreptococcusimmunization relies on macrophages and IFN-γ but not on concurrent adaptive immune responses

“…Instead, we detected accelerated and increased levels of IFN-γ, IL-5 and IL-17, combined with an apparent absence of classical pro-inflammatory cytokines, including IL-6, upon infection of immunized mice. While the cellular source(s) of these cytokines remains elusive, the cytokine profile imprinted by the ip immunizations with HK wt GAS seems to be in line with a possible involvement of ILC populations, including IFN-γ producing memory-like NK cells and possibly trained ILC2 and ILC3 producing IL-5 and IL-17, rather than myeloid subsets [44, 45]. IFN-γ producing tissue resident NK cells are indeed present in the peritoneal cavity [46] and it seems possible that NK cell-derived IFN-γ increases the bactericidal capacity of macrophages in the immunized mice, thus restricting bacterial growth and dissemination, and promoting survival after infection [47, 48].…”

Exploration of the molecular characteristics and potential clinical significance of shared immune-related genes between preterm preeclampsia and term preeclampsia

“…CXCR6 is a member of the CXC chemokine receptor family, and CXCL16 is its ligand with high speci city. Current studies suggest that CXCL16/CXCR6 are mainly involved in the recruitment of decidual T lymphocytes and monocytes, promote endometrial decidualization under pregnancy conditions [20][21][22][23]. Activation of PIK3CB involves multiple signaling cascades of cell growth, survival, proliferation, etc.…”

The Role of Reactive Species on Innate Immunity

“…Mammals possess at least four populations of innate lymphoid cells ILCs that participate in innate immunity: natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells [ 51 ]. NK natural killer cells are innate lymphoid cells optimized to kill virus-infected cells, and can even kill abnormal cells, which do not express MHC class I major histocompatibility complex molecules [ 52 ].…”