Identification of diverse innate lymphoid cells in human decidua

Abstract

Innate lymphoid cells (ILCs) are developmentally related cells that play an important role in innate defenses and tissue remodeling. So far, only natural killer (NK) cells have been identified and functionally characterized in human decidua where they contribute to induction of immune suppression, neo-angiogenesis, and tissue building/remodeling. The presence of other ILC subsets in human decidua has not been yet characterized. Here we identify in human decidua, during early pregnancy, two subsets of decidual group 3 ILC (ILC3), including lymphoid tissue inducer (LTi)-like cells and natural cytotoxicity receptors (NCRs)(+)ILC3 and interferon-(IFN)γ-producing ILC1, different from NK cells. Decidual LTi-like cells produced interleukin -17 (IL-17) and tumor necrosis factor (TNF), while NCR(+)ILC3 released IL-22 and IL-8. Importantly, NCR(+)ILC3 and LTi-like cells established functional interactions with stromal cells. Decidual LTi-like cells differentiated into NCR(+)ILC3, whereas they marginally contributed to NK cell generation. Our data suggest that decidual ILC3 may play a role in innate defenses and in vessel and tissue building, thus contributing to maintenance of pregnancy.

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

“…Adult ILC3 are also responsible for tissue homeostasis and are mainly located in the intestinal lamina propria and tonsils [15]. More recent studies revealed their presence in skin and decidual tissue [21,22]. Different from NK cells, the other ILC subsets are devoid of cytolytic activity and of the ability to exert a direct anti-tumor activity.…”

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

“…The comparable shift in NK-cell immunity has been reported during normal pregnancy including a bias to NKr1 that produce IL-10 in peripheral blood, and NK3 cells that produce TGF-β in decidual NK cells [8]. Additionally, decidual innate lymphoid cell 3 (ILC3) may play a role in innate defenses, and vessel and tissue rebuilding, thus contributing to maintenance of pregnancy [9]. Contrarily, a propensity to Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with RPL and multiple implantation failures (MIF) after in vitro fertilization and embryo transfer cycles [10].…”

NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

“…Notably, ILC subpopulations produce an array of cytokines that in variety match those of T-helper cell subsets. Besides conventional NK (cNK) cells, an additional ILC population expressing NCRs, but functionally different from NK cells, has been identified in both humans [18][19][20][21][22] and mice [23][24][25] . Unlike NK cells, in humans this NCR þ cell population is dependent on the orphan nuclear receptor (ROR)gt transcription factor and on the interleukin (IL)-7Ra for its development and function.…”