Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells

Abstract

A successful pregnancy requires many physiological adaptations from the mother, including the establishment of tolerance toward the semiallogeneic fetus. Innate lymphoid cells (ILCs) have arisen as important players in immune regulation and tissue homeostasis at mucosal and barrier surfaces. Dimensionality reduction and transcriptomic analysis revealed the presence of two novel CD56 Bright decidual ILCs that express low T-bet and divergent Eomes levels. Transcriptional correlation with recently identified first trimester decidual dNKs suggests that these novel decidual ILCs might be present throughout pregnancy. Functional testing with permutation analysis revealed production of multiple factors by individual cells, with a preference for IFNγ and VEGF. Overall, our data suggests continuity of a unique decidual innate lymphocytes across pregnancy with a polyfunctional functional profile conducive for pregnancy

Transcriptional and functional characterization of neonatal circulating Innate Lymphoid Cells

“…Of note, in addition to CB‐derived ILCs, various distinct innate lymphocyte subsets were recently defined in the decidua (d) such as dILC3, dLTi, and dILC1, along with various novel NK cell subsets 61‐63 . Functionally and phenotypically, dILCs resemble other tissue‐specific ILCs rather than CB‐derived ILCs.…”

“…3 Of note, in addition to CB-derived ILCs, various distinct innate lymphocyte subsets were recently defined in the decidua (d) such as dILC3, dLTi, and dILC1, along with various novel NK cell subsets. [61][62][63] Functionally and phenotypically, dILCs resemble other tissue-specific ILCs rather than CB-derived ILCs. dILC3 for example functionally and phenotypically resemble tonsillar ILC3 by secretion of IL-22 and expression of surface molecules such as CCR6, IL23R, and NKp44, whereas dILC1 resemble intraepithelial ILC3, which express CD103 and share NK cell surface molecules.…”

“…dILC3 for example functionally and phenotypically resemble tonsillar ILC3 by secretion of IL-22 and expression of surface molecules such as CCR6, IL23R, and NKp44, whereas dILC1 resemble intraepithelial ILC3, which express CD103 and share NK cell surface molecules. [61][62][63] Therefore, despite their anatomical proximity, CB ILCs do not resemble dILCs and have a unique transcriptomic phenotype.…”

Multiomic analysis reveals decidual‐specific transcriptional programing of MAIT cells

“…23 Decidual tissue was mechanically and enzymatically dissociated as previously described. 24,25 were isolated from whole blood via density gradient centrifugation.…”

Killer Timing: The Temporal Uterine Natural Killer Cell Differentiation Pathway and Implications for Female Reproductive Health

“…ILC subsets are categorised according to their cytokine profiles and transcription factor expression: ILC1s express T-bet and secrete IFN-g; ILC2s express GATA-3 and secrete IL-5, IL-9 and IL-13; and ILC3s, which include a lymphoid tissue inducer-like subset, are defined by their expression of RORgt and secrete IL-17 and IL-22. Natural killer (NK) cells are known as key members of the ILC family, although it remains to be clarified whether tissue-resident NK cells in the uterine mucosa constitute a unique NK cell population or denote a population that includes ILC1s and ILC3s (7,8). NK cells represent the predominant maternal immune cell component in the secretory stage endometrium and comprise up to 70% of leukocytes in first trimester decidua: they promote critical changes in the uterine microenvironment both during the 'window of implantation' and in early pregnancy (9)(10)(11), and uterine NK numbers subsequently diminish from mid-gestation to term (12).…”