Composition, Development, and Function of Uterine Innate Lymphoid Cells

Abstract

Innate lymphoid cells (ILCs), including NK cells, contribute to barrier immunity and tissue homeostasis. In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology. In this article, we report on the composition of uILCs in the endometrium during the luteal phase and in the decidua during early pregnancy. Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR+ and partially overlap with previously described IL-22–producing uterine NK cells. Development of mouse uILC3 is Nfil3 independent, suggesting unique features of uILCs. Indeed, although the cytokine production profile of mouse uILCs recapitulates that described in other tissues, IL-5, IL-17, and IL-22 are constitutively produced by uILC2s and uILC3s. This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy.

NK cells and type 1 innate lymphoid cells: partners in host defense

“…When assayed ex vivo, these decidual NK cells have low lytic activity but are characterized by secretion of cytokines and chemokines that may shape the decidual vasculature during pregnancy. Similarly, NK cells, as well as ILC1s, ILC2s and ILC3s, are found in the uterine tissues of mice 16 .…”

NFIL3 Expression Distinguishes Tissue-Resident NK Cells and Conventional NK-like Cells in the Mouse Submandibular Glands

“…While cNK cells depend on NFIL3 for development, trNK cells in the liver, skin, kidneys, and uterus develop mostly independently of NFIL3 (3, 10). It was also recently reported that salivary gland NK cells develop entirely independently of NFIL3 activity (22, 23).…”

Uterine Natural Killer Cells: Functional Distinctions and Influence on Pregnancy in Humans and Mice

“…Other than uNK cells, first defined in 1991, ILC1s and ILC3s have also been identified in human decidua (2, 33, 69, 70). Uterine ILC3s (uILC3s) were initially classified as stage 3 uNK cell progenitors based upon their CD34 − CD117 + CD94 − CD56 + KIR − phenotype.…”

“…uNK cells in mice can now be classified as CD49a + DX5 +/− uterine tissue-resident NK (trNK) cells and CD49a − DX5 + uterine conventional NK (cNK) cell populations (33, 48, 58, 59), which will be described in greater depth later in this review. DBA reactivity is strongest on uterine CD49a + trNK, and is weak on DX5 + uterine cNK (40, 58).…”